Bone Neoplasms
Bone neoplasms are tumorous formations that develop as a result of the loss of normal growth and proliferation control in the cells that make up the skeletal system. The clinical effects of these neoplasms may not be limited to the bone tissue itself. Depending on the tumor's location and its relationship with surrounding tissues, movement and muscle function may be impaired, neurological signs may develop, and lesions arising in certain regions of the axial skeleton may affect respiratory function.
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Definition
Classification of Bone Tumors
Bone tumors are classified based on the cell type from which they originate and the matrix they produce. Osteosarcoma (OSA) is a malignant neoplasm arising from primitive bone cells capable of producing osteoid matrix. Chondrosarcoma (CSA) originates from anaplastic cartilage cells that produce cartilage matrix. Hemangiosarcoma (HSA), a malignancy of vascular origin, is characterized by the proliferation of neoplastic endothelial cells. The primary histological feature of fibrosarcoma (FSA) is the presence of neoplastic fibroblasts within a collagenous matrix. Multilobular osteochondrosarcoma (MLO), which has a distinct morphology, consists of multiple lobules of bone or cartilage matrix surrounded by thin layers of spindle-shaped cells.
Etiology and Pathophysiology
The development of primary bone tumors cannot be attributed to a single cause. However, particularly in dogs, the markedly higher incidence of osteosarcoma in certain breeds suggests that genetic predisposition may be an important factor in disease development.
This genetic predisposition does not have the same characteristics across all breeds. A single-gene-associated risk factor has been identified in the Scottish Deerhound, while the CDKN2A/B locus is thought to be associated with disease development in Leonbergers and Greyhounds. In some other breeds, variations in the GRB10 gene have also been shown to play a role.
Nevertheless, osteosarcoma susceptibility across the canine population is considered to have a much more complex genetic basis, with relevant factors varying among different breed groups.
In osteosarcoma cells, genetic predisposition is not the only factor involved; various molecular alterations may also arise during tumor development. Abnormalities involving tumor suppressor systems such as p53, retinoblastoma, and PTEN, as well as alterations in signaling mechanisms associated with MET, insulin-like growth factor, erbB-2, and mTOR, have been identified.
These alterations may disrupt normal signaling pathways that regulate cellular growth, proliferation, and survival, ultimately contributing to uncontrolled cellular proliferation.
In addition to genetic factors, certain clinical and environmental conditions have also been reported to be associated with the development of bone sarcomas. For example, an association between early-age gonadectomy and an increased risk of bone sarcoma has been demonstrated in Rottweilers; however, the biological mechanism underlying this relationship has not yet been fully established.
Different associations between gonadal status and OSA risk have been reported in other breeds and populations. This indicates that the relationship between gonadectomy and osteosarcoma cannot be interpreted in the same way for all dogs.
Chronic damage or pre-existing alterations in bone tissue have also been associated with tumor development in some cases. Osteosarcoma may develop at sites containing orthopedic metal implants, areas affected by chronic osteomyelitis, and bones with previously sustained and healed fractures. This has been reported both in fractures treated with internal fixation and in cases managed without fixation.
Osteosarcoma is also among the late complications that may develop following radiotherapy, and this has been reported in both dogs and cats.
In addition, various bone sarcomas, including OSA, CSA, and FSA, may develop in association with previously occurring bone infarcts.
Some bone lesions that initially exhibit benign characteristics may undergo malignant transformation over time. Cartilaginous exostoses and bone cysts are among the lesions in which malignant transformation has been reported.
Primary Bone Tumors
When neoplasms arising in the bones of dogs and cats are evaluated, malignant tumors are more common than benign bone tumors.
Primary bone neoplasms can be classified according to their tissue of origin into mesenchymal, vascular, or hematopoietic groups.
The major primary tumors of mesenchymal origin include osteosarcoma, chondrosarcoma, and fibrosarcoma. Hemangiosarcoma is a malignant bone tumor of vascular origin, while lymphoma and osseous plasmacytoma are examples of hematopoietic bone neoplasms.
In dogs, osteosarcoma is by far the most common primary bone tumor.
All other primary malignant bone tumors, including CSA, FSA, HSA, MLO, lymphoma, and osseous plasmacytoma, collectively account for less than 15% of skeletal malignancies.
The anatomical distribution of primary malignant bone tumors can be broadly evaluated according to two major regions: the appendicular and axial skeleton.
In the appendicular skeleton, osteosarcoma development is particularly concentrated in the metaphyseal regions of long bones. The distal radius and proximal humerus are characteristic sites. The distal femur and the proximal and distal metaphyseal regions of the tibia are also frequently affected.
In the axial skeleton, the tumor type may vary according to anatomical location:
Skull: MLO and OSA
Mandible and maxilla: OSA
Ribs: OSA, CSA, and HSA
Vertebrae: OSA and CSA
Pelvis: OSA and CSA
Osteosarcoma does not always originate from the medullary portion of the bone. Periosteal and parosteal forms of osteosarcoma, which develop on the bone surface, have also been described.
More rarely, osteosarcoma may arise outside the skeletal system. This form, known as extraskeletal osteosarcoma, can develop in non-osseous tissues such as the liver, spleen, kidneys, mammary glands, gastrointestinal tract, or subcutaneous tissues.
Secondary Bone Neoplasms
A malignant lesion detected in bone does not necessarily originate from the bone itself. Malignant neoplasms arising from other tissues may reach the skeletal system through the bloodstream or by direct invasion, resulting in secondary bone tumors.
Neoplasms known to metastasize to bone include mammary carcinoma, urothelial carcinoma, prostatic adenocarcinoma, and pulmonary carcinoma. Bone metastases resulting from neoplasms originating in the spleen and tonsils have also been reported.
In studies evaluating metastatic bone neoplasms, carcinomas and hemangiosarcoma are among the commonly identified primary tumors.
The primary route by which metastatic cells reach the bone is hematogenous spread. However, a malignant mass located close to bone may also extend through surrounding tissues and directly invade the bone.
The distribution of metastatic lesions in long bones may differ from that of primary bone tumors. Metastases may preferentially affect the diaphyseal regions, and this distribution is thought to be associated with the anatomical location of the nutrient foramina.
The femur and humerus, followed by the ribs, pelvis, and lumbar vertebrae, are among the sites where metastatic bone disease is frequently reported.
Therefore, when an aggressive lesion is detected in bone, the diagnostic evaluation should not focus exclusively on osteosarcoma and other primary bone tumors. Particularly in patients with a concurrent malignancy or a previous history of neoplasia, secondary bone involvement should be considered an important part of the differential diagnosis.
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