Osteosarcoma

Chapter 87


Osteosarcoma




Appendicular osteosarcoma (OSA) is the most common primary bone tumor in dogs, accounting for approximately 75% to 80% of focal malignant bone lesions. Arising from transformed osteoblasts, OSA frequently develops within the metaphyseal regions of long bones. OSA tends to affect middle-aged to older dogs (7 to 10 years); however, some reports describe an additional incidence peak at 2 years of age. Unlike some tumors, OSA shows an incidence that only subtly favors males, with a reported male : female ratio of 1.5 : 1. Specific breeds with large skeletal mass, including Saint Bernards, rottweilers, Great Danes, greyhounds, and Labrador retrievers, appear to be at increased risk of OSA development.



Diagnosis



History and Physical Examination


The most common sites of OSA development are the distal radius, proximal humerus, and proximal tibia. Given these anatomic sites, dogs with appendicular OSA commonly are brought to the veterinarian because of acute or chronic lameness and limb swelling. Clinical signs of lameness often are associated temporally with perceived traumatic events such as running, jumping, or rough play with other dogs. In addition to showing varying degrees of lameness, dogs also may have significant peritumoral soft tissue swelling. Following the onset of lameness, some dogs partially improve with symptomatic therapy, including rest, nonsteroidal antiinflammatory drugs, or other analgesics; however, recurrent and progressive bone pain refractory to conservative therapy is common. Dogs with OSA that have had longstanding chronic pain may demonstrate significant discomfort of the affected limb even after minimal or light manipulation.



Imaging Modalities


Despite the increasing availability of advanced imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography, radiography remains the most commonly employed radiologic method for assessing the extent of disease in dogs with OSA. Given that appendicular OSA has the capacity not only for local bone destruction but also for distant metastasis, it is recommended that every dog suspected of having OSA undergo radiography of both the primary tumor site and the thorax. At presentation, the majority of affected dogs have radiographically evident disease at the primary tumor site, typically characterized by a mixed osteolytic-osteoproductive focal lesion arising from the metaphyseal region of long bones. Only a small percentage of dogs (~10%) have radiographic evidence of macroscopic pulmonary metastases at initial presentation; however, the vast majority (>90%) eventually develop radiographically evident pulmonary metastatic disease.


In addition to radiography, various advanced imaging modalities can be used for evaluating the size of the primary tumor or the extent of pulmonary metastasis. For more accurate characterization of primary tumor size and degree of intramedullary involvement, imaging modalities such as CT, MRI, nuclear scintigraphy, and single-photon emission CT can provide supplemental information to ensure that adequate surgical margins are achieved as required for successful limb-sparing surgery. Nuclear scintigraphy is useful not only for assessing the primary tumor but also for identifying additional skeletal lesions distant from the primary tumor. CT is more sensitive than conventional radiography in assessing for pulmonary metastasis and has the ability to identify small metastatic lesions (2 to 3 mm), which are undetectable by conventional radiography. The greater sensitivity of CT for detection of metastasis might allow for improved disease stratification and determination of prognosis in patients diagnosed with OSA (Eberle et al, 2011).



Differential Diagnoses


Differential diagnoses for OSA include other primary bone tumors, bacterial or fungal osteomyelitis, bone metastasis from other primary sites, and systemic diseases that affect bone such as multiple myeloma or lymphoma. Benign processes such as bone cysts and degenerative or active remodeling also can be considered. It is important that a complete history be obtained (including any history of travel to areas of endemic fungal infection) so that the clinician can take into account all factors when making a diagnosis. Radiographic appearance is helpful, especially when there is a classic appearance in a classic location. However, the classic radiographic features of OSA are not present in every case. In addition, other primary bone tumors may have a similar radiographic appearance. Involvement of multiple bones is uncommon in OSA; however, synchronous primary OSAs occasionally can occur. Metastatic disease affecting bone is usually in a diaphyseal location rather than in the metaphysis but can be either lytic or proliferative. The presence of multiple punched-out lesions in several bones suggests multiple myeloma.


The most accurate means to differentiate OSA from other bone diseases is through a bone biopsy. However, because bone biopsy is an invasive procedure and the results are not always available immediately, fine-needle aspiration and cytologic evaluation can be helpful initially to help rule out other differential diagnoses. Most bone tumors have a soft tissue component that yields cells on needle aspiration. A cytologic specimen devoid of inflammation and yielding a population of malignant mesenchymal cells supports the diagnosis of a primary bone malignancy. Osteosarcoma generally cannot be differentiated cytologically from other sarcomas using standard staining methods. Staining of bone tumor aspirates for alkaline phosphatase (AP) activity can be helpful in further characterizing malignant mesenchymal cells as OSA. In one study, AP staining of 61 bone lesion aspirates provided an accurate diagnosis of OSA with 100% sensitivity and 89% specificity (Barger et al, 2005).


The gold standard for diagnosis remains biopsy. There are several methods for obtaining bone tissue for analysis. The two most common techniques are closed biopsy using a Jamshidi bone marrow biopsy needle and open biopsy using a trephine or curette. Both methods require general anesthesia, and regional radiographs or fluoroscopy should be available to aid the clinician in selecting an appropriate area within the tumor from which to collect the specimen. Attempts should be made to obtain a sample from the center of the radiographic lesion. The advantages of needle biopsy are that the procedure can be done through a single tiny stab incision without a surgical approach. The resulting bone defect is small, typically involving a single cortex, and therefore is unlikely to initiate a pathologic fracture. The disadvantage of the closed technique is the relatively small sample obtained. An open biopsy using a trephine requires a surgical approach and creates a bigger defect through both cortices; however, the sample obtained is larger. The downside of this technique is that there is a higher potential risk of pathologic fracture. Regardless of the method used to obtain the specimen, it is important to send the tissue to an experienced pathologist with expertise in bone pathology.


It must be emphasized to clients that no diagnostic test is 100% accurate. A diagnosis of reactive bone is not uncommon on preoperative biopsy of an OSA, regardless of whether the specimen is obtained by needle or trephine. In cases in which the histopathologic interpretation does not match the clinical picture, OSA should not be ruled out. In some cases second, larger biopsy specimens still yield reactive bone; yet when the entire lesion is submitted following definitive surgery, the pathologist can readily make a diagnosis of OSA. Similarly, one should be cautious when interpreting bone biopsy results indicating the presence of a primary bone fibrosarcoma, chondrosarcoma, or hemangiosarcoma. Although these other primary tumors do occur on occasion, OSA is far more common.



Biologic Behavior


Appendicular OSA is associated with two distinct life-limiting pathologic processes: local invasion and distant metastases. Although OSA arises from the medullary cavity, it rapidly grows eccentrically, which results in the invasion and destruction of surrounding trabecular and cortical bone with eventual soft tissue involvement.


Although local tissue destruction is a hallmark of OSA, several effective management strategies can limit the morbidity associated with the localized invasive properties of OSA. For this reason, the major life-limiting barrier for dogs diagnosed with OSA is the development of distant metastases. The pulmonary parenchyma is the most common metastatic site, whereas involvement of regional lymph nodes appears relatively uncommon (Hillers et al, 2005). Pulmonary metastatic lesions usually appear as discrete soft tissue nodules, and multiple lesions are common. Additional sites of metastases include bone, skin, and other extraskeletal sites.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Osteosarcoma

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