Outline of Veterinary Skeletal Pathology

contents Ch 2, p 6 Chapter 2, Page 7 Ch 3, p 1 

Outline of Veterinary Skeletal Pathology

Chapter 2 - Bone, Pathologic Conditions

F. Neoplastic and Neoplastic-like Conditions

1. Neoplastic-like conditions. One must be careful to distinguish neoplasms from tumor-like lesions that are infrequently associated with bone and joints. Some examples of tumor-like lesions that may cause confusion are: simple or unicameral bone cysts (figs. Ib6-1, Ib6-2, Ib6-3), aneurysmal bone cysts (fig. Ib6-4), fibrous dysplasia (fig. Ib1-12), central giant cell granuloma, pigmented villonodular synovitis, nodular tenosynovitis, or "ganglion." Epidermal inclusion cysts and epidermoid cysts may be found deep in vertebrae at the midline of Rhodesian Ridgeback dogs (a congenital abnormality), or epidermal inclusion cysts may be found in the nail bed and involve the third phalanx.

2. Neoplastic conditions.
a. Benign disorders.
(1) osteoma. This is an uncommon tumor occurring most frequently in the head. The tumor may arise at any age and is seen as a solitary lesion.
(a) clinical feature. The tumor shows slow progressive growth and usually does not cause pain (fig. Ib6-5).
(b) pathology.
(i) osteoma is formed by intramembranous bone formation.
(ii) it is attached to the bone's surface by a broad base; and when mature, is difficult to distinguish from an osteophyte.
(iii) it is composed of cancellous bone and fibrous connective tissue, or fat fills marrow spaces.
(iv) the matrix may have a mucoid appearance.
(v) the periosteum is well differentiated and composed of fibrous and osteogenic (cambium) layers.
(vi) peripheral trabeculae are composed of woven bone bordered by typical osteoblasts.
(2) ossifying fibroma. A rare fibro-osseous tumor of the jaw of horses and cattle.
(a) clinical feature. This tumor generally arises in the maxilla or mandible and forms a large round non-painful protuberance (fig. Ib6-6). Occasionally it occurs within the sinuses.
(b) pathology.
(i) it is a sharply demarcated lesion, and the rapidly expanding mass distorts the bone's normal contour (figs. Ib6-7, Ib6-8).
(ii) normal bone is replaced by a fibro-osseous stroma composed of irregular trabeculae of osteoid and woven bone rimmed by osteoblasts (fig. Ib6-9).
(iii) the lesion can be differentiated from osteoma because the intervening connective tissue is more cellular and contains more collagen fibers than does osteoma.
(iv) also, there is no truly recognizable periosteal membrane (fig. Ib6-10).
(3) chondroma. Benign forms of cartilaginous tumor are not frequent, but are reported. When this tumor arises within the medullary cavity, it is termed an enchondroma.
(4) enchondroma is a benign cartilage tumor that arises within the medullary cavity.
(a) clinical features. Primary chondromas form masses in bone or cartilage.
(b) pathology. Chondromas are distinguished from chondrosarcoma by their lack of local invasiveness, more orderly arrangement of the cartilage cells, and closer resemblance to normal mature cartilage. They should be distinguished from lesions occurring in mixed tumors, multilobular tumor, synovial or bursal chondromatosis, and osteochondroma.
(5) osteochondroma (multiple cartilaginous exostoses, chondrodysplasia, diaphyseal aclasis, hereditary deforming chondrodysplasia).
(a) clinical features. Exophytic osseous lesion that usually occurs in the metaphyses of young animals and ceases to grow when the animal becomes mature (fig. Ib6-11). The condition is more common in dogs, cats, and horses and may be monostotic (solitary) or polyostotic (osteochondromatosis).
(b) pathology. Osteochondromas are thought to arise from ectopic growth-plate cartilage.
(i) cartilaginous growth seems to be the initial factor, followed by endochondral ossification. This results in a cartilage capped lesion, but the cartilage cap may disappear as the lesion matures (figs. Ib1-10, Ib1-11).
(ii) cartilage usually persists around the periphery of the tumor.
(iii) histologically, the lesion points away from the joint, and the cortex and spongiosa of the osteochondroma blend imperceptibly with the cortex and spongiosa of the host's bone.
(iv) when lesions are removed from their primary location, the lesion cannot be distinguished from marginal osteophytes which occur secondary to osteoarthritis.
(v) malignant transformation to chondrosarcoma has been reported in three dogs. Senescent osteochondromas may have the cartilage cap completely replaced by bone.
(6) fibroma.
(a) clinical features. These tumors are extremely infrequent as primary tumors of bone, but have been reported.
(b) pathology. They are circumscribed, usually encapsulated, and made up of more mature collagenous connective tissue. Their course is benign, although they may be locally disfiguring.
(7) other tumors.
1. chordomas are rare malignant tumors of bone and soft tissue that arise along the axial skeleton. They are reported most frequently in the lumbosacral or coccygeal region of ferrets, ranch mink, and rats.
2. Hemangiomas are infrequent primary bone tumors.
3 Other primary bone tumors such as schwannoma are extremely rare. Osteoblastoma has been reported in the radius of a horse, and a related tumor, osteoid osteoma, has been reported in the vertebra of a cat.
b. Primary malignant tumors. Osteosarcoma is the most frequent bone neoplasm, and in different studies is reported to represent between 65% and 85% of the primary bone neoplasms of the dog. Chondrosarcomas are the next most common primary bone tumor (15%) with fibrosarcomas and hemangiosarcomas occurring about equally. Osteosarcoma and fibrosarcoma are occasionally found as a solitary lesion in a long bone of small breed dogs that have infarcts in multiple bones (figs. Ib6-12, Ib6-13). Liposarcomas are uncommon, and malignant mesenchymoma and leiomyosarcomas are rare.
(1) osteosarcoma (osteogenic sarcoma).
(a) incidence. Osteosarcoma is the most common primary bone tumor of domestic animals. They occur in most species, but they are more frequent in the dog, especially in giant breeds.
(b) etiology. The etiology is unknown, but tumors appear to arise at sites of high bone turnover. The suspected roles of trauma and viral disease are not clearly established.
(c) clinical features.
(i) Osteosarcomas arising within the bone originate most often in the metaphysis of long bones where bone turnover is greatest, even after physeal plate closure. But, osteosarcoma may arise from any site, including the sesamoids (fig. Ib6-14). About 20 percent of osteosarcomas occur in the dog's axial skeleton. Osteosarcoma of the head is more frequent in the bovine and horse.
(ii) periosteal osteosarcomas arise from the surface of the bone, more frequently from the diaphysis than from the metaphysis, and are neoplasms of intermediate differentiation.
(iii) parosteal (juxtacortical) osteosarcomas are tumors that arise on the surface of the bone and do not involve the medullary cavity. They are typically composed of well-differentiated but malignant fibro-osseous tissue. Parosteal osteosarcomas are very rare, are not prone to metastasize, but recur locally after incomplete removal.
(iv) extraskeletal osteosarcoma are uncommon tumors; and in dogs, they arise most often in visceral organs.
(d) pathology.
(i) macroscopic appearance. These tumors may appear as either a large metaphyseal necrotic and hemorrhagic mass (fig. Ib6-15) or as a more proliferative lesion that expands beyond the metaphyseal cortical boundary (fig. Ib6-16). Tumor invasion of the end of the bone is usually blocked by epiphyseal cartilage, and osteosarcoma rarely extends into the nearby joint space.
(ii) microscopic appearance.
(a) types. Histopathologic variations include patterns with various predominating features: sclerosis, cartilage (figs. Ib6-17, Ib6-18), spindle cells (fig. Ib6-19), large cells (fig. Ib6-20), giant cells, small or round cells, and vascular or cyst-like (telangiectatic osteosarcoma)(figs. Ib6-21, Ib6-22, Ib6-23).
(b) essential feature. The diagnosis of osteosarcoma is dependent upon recognizing that there is production of osteoid and/or woven bone by unequivocally neoplastic stromal cells (fig. Ib6-24).
(c) defining characteristics. The characteristic of osteosarcoma is the presence of neoplastic osteoblasts that appear histologically as short, spindle-, or triangular-shaped cells with plump ovoid nuclei, usually closely packed together. The cells do not lie parallel to one another in bundles but point in various directions (figs. Ib6-25, Ib6-26). The critical identifying characteristic of these cells is their ability to produce osteoid, the collagenous matrix that may or may not become mineralized to form bone. Newly formed osteoid is extracellular, dense, and deeply eosinophilic and may be somewhat fibrillar. Osteocytes may be trapped within it, a feature also of normal bone. Multinucleated cells may also be present and can be identified as both osteoclasts and tumor giant cells. The recognition of newly formed osseous tissue as being an osteosarcoma is dependent upon identification of anaplastic characteristics of osteoblasts which on rare occasions may not be obvious. In these cases, helpful diagnostic features include tumor filling the intertrabecular spaces, osteoid production as streamers and globules of unmineralized matrix, neoplastic cartilage, and global bone resorption in radiographs.
(iii) behavior. In the dog, osteosarcoma of the skull, including paranasal sinuses or calvarium, generally has a longer clinical survival time than osteosarcoma of the limbs (fig. Ib6-27). Osteosarcomas metastasize to the lung very early, and the lung lesions may cause hypertrophic pulmonary osteoarthropathy, which may add to the difficulty of interpreting a bone biopsy. Approximately 10% of osteosarcomas metastasize to other bones.
(2) multilobular tumor (multilobular osteoma/chondroma, multilobular osteo/chondrosarcoma, chondroma rodens, cartilage analogue of fibromatosis, juvenile aponeurotic fibroma). This tumor consists of multiple small compact osteocartilaginous lobules usually arising in the canine skull (figs. Ib6-28, Ib6-29).
(a) incidence. These tumors are uncommon but not rare.
(b) clinical features. Although it usually arises in the head of dogs, it occurs in other bones and has been seen in cats and horses. It is a distinct tumor type that has unique morphologic features. Radiographic study reveals rather diffuse nodular or stippled densities in soft tissues around the skull (fig. Ib6-28). Densities are accompanied by rarefaction of the underlying cranial bones.
(c) pathology.
(i) macroscopic appearance. The lesion begins as a small protuberance; but if left untreated, it can become massive (fig. Ib6-30).
(ii) microscopic appearance. Microscopic examination reveals small islands of chondroid, osseous, or osteocartilaginous tissue surrounded by spindle-shaped cells in connective tissue (figs. Ib6-31, Ib6-32). Foci of calcification may be seen in the fibroblastic cells. This lesion is potentially aggressive, and increased numbers of mitotic figures, less distinct lobulation, and overgrowth of one of the mesenchymal components suggest malignancy. Multilobular sarcomas should be differentiated from the standard variety of chondrosarcoma or osteosarcoma.
(iii) behavior. The disease causes progressive local tissue destruction, and the tumor has a high rate of metastasis. If not completely excised, local lesions can recur and may metastasize to the lung.
(3) Chondrosarcoma.
(a) incidence. In the dog, chondrosarcomas are second in frequency to osteosarcomas.
(b) clinical features. Chondrosarcoma tends to arise from sites where normal cartilage exists, such as near rib cartilage, scapular cartilage, pelvis, and the nasal turbinates and septum. There is local swelling and pain. Radiographs show bone destruction and occasional medullary involvement with mottled densities.
(c) pathology.
(i) macroscopic appearance. The tumor appears as a lobulated white or gray mass that contains mucoid material (fig. Ib6-33). Foci of calcification and ossification appear as popcorn-like densities in radiographs.
(ii) microscopic appearance. This tumor is made up of irregular, disorderly masses of immature cartilage (fig. Ib6-34) that invade tissue and metastasize through the lymphatic and blood circulation. Tumor may infiltrate between host bone trabeculae before the trabeculae are resorbed or altered by remodeling. The cartilage cells in lacunae of cartilaginous matrix vary in size and do not maintain any orderly polarity (fig. Ib6-35). Because of the tendency of normal cartilage cells to become hypertrophic during the process of endochondral ossification, it is difficult to use cell or nuclear size as the main criteria of malignancy for cartilage tumors. In addition to nuclei becoming enlarged, they become hyperchromatic; and they develop other diagnostic features of malignancy such as having double nuclei per cell, large eosinophilic nucleoli, and multiple enlarged nucleoli. Perhaps one of the most helpful features is cellular disorganization. Malignant cartilage lobules are often separated by bands of fibrous tissue. Malignancy is also evidenced by tumor invasiveness and tendency to metastasize to the lungs and elsewhere.
(iii) types of chondrosarcoma include those composed of hyaline cartilage of a fibromyxoid variety (mesenchymal chondrosarcoma)with myxoid fibrillary material. Mesenchymal chondrosarcomas are highly malignant tumors in which a large proportion of the tumor is composed of primitive spindly to ovoid mesenchymal stromal cells.
(iv) distinction between chondrosarcoma and osteosarcoma. Chondrosarcomas can contain regions of osseous metaplasia (chondroid bone)(fig. Ib6-36), and neoplastic cartilage is commonly found in osteosarcomas. In order to distinguish chondrosarcoma from osteosarcoma, one should determine that the osteoid is not produced directly by malignant stromal cells and that it first goes through a cartilage phase.
(d) behavior. Chondrosarcomas are also quite malignant and tend to recur when excised. Surgical removal is slightly more successful with chondrosarcoma than osteosarcoma.
(4) fibrosarcoma. This tumor may arise from connective tissue anywhere in the body and occasionally is primary in bone (fig. Ib6-37).
(a) incidence. The third most common tumor of the appendicular skeleton.
(b) clinical features. Quite commonly an extraskeletal fibrosarcoma invades bone (figs. Ib6-38, Ib6-39). When the tumor arises from within the bone, it produces localized swelling and pain.
(c) pathology. The cells are pleomorphic and vary from highly undifferentiated, roughly spindle-shaped cells with round to ovoid nuclei, often in mitosis, to elongated cells that form interlacing bundles resembling immature connective tissue. This tendency for groups of cells to be parallel to one another is a feature of value in identifying fibrosarcoma (fig. Ib6-40).
(d) behavior. Fibrosarcomas usually do not metastasize even after several months, but they may be associated with bone lysis and local extension. Canine fibrosarcomas of the maxilla are tumors of low-grade malignancy that arise on the outer bone surface and must be differentiated from invasive amelenotic melanomas.
(5) hemangiosarcoma (malignant hemangioendothelioma). A tumor arising from endothelium.
(a) incidence. Hemangiosarcoma may be primary in almost any tissue, but in most species it more frequently originates in spleen, liver, heart muscle (atrium) and bone.
(b) clinical features. Primary osseous hemangiosarcoma most commonly arises in long bones where it causes swelling and pain.
(c) pathology.
(i) macroscopic appearance. It causes expansion of the bone and in a bone slice appears as a very hemorrhagic mass (fig. Ib6-41).
(ii) microscopic appearance. The histologic features include neoplastic cells with large hyperchromatic nuclei and scant cytoplasm. The cells tend to form vascular spaces, often quite large, which may be distended with blood (fig. Ib6-42). The blood vessels are clearly formed by tumor cells and are not part of the supporting stroma. Mitoses are common.
(d) Behavior. These are highly malignant neoplasms. Metastases can be expected, and tumor may be found in multiple sites. These tumors destroy bone locally as do osteosarcomas and chondrosarcomas, and they metastasize just as readily.
(6) liposarcoma.
(a) incidence. Only a few primary liposarcomas of bone have been reported.
(b) clinical features. There may be localized swelling and pain.
(c) pathology. The tumor may appear as gray fatty tissue replacing bone marrow. Microscopically, liposarcomas are distinguished from other primary sarcomas by being composed of neoplastic adipocytes (figs. Ib6-43, Ib6-44). In the diagnosis of liposarcoma, caution must be taken to make sure that the lipid vacuoles are within neoplastic cells. Other types of sarcomas can invade normal fatty marrow and mimic liposarcoma.
(d) behavior. Unknown because of sparsity of reports.
(7) giant cell tumor of bone (osteoclastoma).
(a) incidence. This tumor is rarely encountered in dogs and cats.
(b) clinical features. This tumor causes bone destruction like an osteosarcoma, but it generally arises in the epiphysis rather than the metaphysis.
(c) pathology.
(i) macroscopic appearance. It occurs as an eccentric epiphyseal lesion of long bones and usually is confined within bone, being covered by a thin rim of osseous tissue.
(ii) microscopic appearance. Histologically, the tumor is composed of ovoid or short spindly stromal cells with masses of prominent osteoclast-like giant cells (fig. Ib6-45). True osteoclasts stain for tartrate resistant acid phosphatase. Nuclei in the mononuclear and giant cells appear similar, are ovoid to reniform, contain small nucleoli, and have a finely stippled chromatin pattern. This tumor must be differentiated from other lesions containing giant cells, such as a simple bone cyst, aneurysmal bone cyst, hyperparathyroidism, fibrous dysplasia, giant cell variants of osteosarcoma, and reparative granuloma.
(d) behavior. There are too few tumors reported in animals to discuss behavior. However, until further information is obtained, they should be considered tumors of low malignancy.
(8) secondary tumors of bone. Malignant neoplasms may metastasize to bone from primary sites, which include mammary gland, lung, urinary tract, oral mucosa, skin and subcutis, thyroid, and bone.
(a) incidence. Metastasis to bone is not as frequent as to lung or liver.
(b) clinical features. The clinical manifestations of secondary tumors in bone include: lameness, pain, swelling, and less frequently, paraplegia. The radiographic appearance is often indistinguishable from a primary tumor. For example, secondary (metastatic) tumors may localize near the epiphysis, expand extensively, and be radiolucent. Sometimes they may contain spicules of bone. Definitive diagnosis is based on histologic examination.
(c) pathology. Some neoplasms arising adjacent to bone may either invade the bone or alter it by compression. Squamous cell carcinomas arising in the oral or pharyngeal mucosa may invade the mandible or maxilla, although their usual route is to the retropharyngeal lymph nodes and then to lungs. Rhabdomyosarcoma and malignant fibrous histiocytoma invade bone. Neoplasms of hemopoietic cells may originate in and displace the bone marrow. Lymphosarcoma and histiocytic lymphoma (figs. Ib6-46, Ib6-47) tend to replace bone marrow and may cause bone infarction. Plasma cell tumors may occur as solitary lesions and may expand the medullary cavity, destroy the cortex, and extend into adjacent tissue (figs. Ib6-48, Ib6-49, Ib6-50). Alternatively, plasma cell tumors may take the form of multiple myeloma where it forms multicentric lytic lesions that have a characteristic radiographic appearance of a "punched-out" lesion without a sclerotic margin.

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