History
A 14-year-old spayed female mixed-breed cat was evaluated at a private clinic in Cluj-Napoca, Romania, because of progressive swelling over the proximal portion of the left humerus and severe lameness both of 2 months’ duration.
Clinical and Gross Findings
On physical examination, the cat had swelling and deformation of the left shoulder joint region, with joint immobility and local sensitivity. During the examination, the cat also had prolonged episodes of right-sided recumbency, became progressively weaker, and developed respiratory failure. Severe proptosis of the left globe with epiphora, episcleral hyperemia, corneal edema, mild glaucoma, signs of pain, and apparent loss of visual acuity was also present. A lateral radiographic view of the left shoulder joint region revealed a radiating pattern of bony proliferation and destruction that was centered on the proximal aspect of the humerus and extended into the adjacent soft tissues. Multiple nodules (1 to 3 cm in diameter) were visible throughout the pulmonary parenchyma. Because of the poor clinical prognosis, the cat was euthanized by IV injection of a combination solution of embutramide, mebezonium iodide, and tetracaine hydrochloride and submitted for necropsy.
Postmortem examination revealed a gray-white, well-demarcated, lobular ovoid mass (11 × 10 × 8 cm) that extended from the proximal aspect to the mid-diaphyseal area of the left humerus. The cut surface of the mass contained multiple individual and coalescing firm, gritty areas (Figure 1). Muscle atrophy and edema were present adjacent to the tumor. No neoplastic invasion of the shoulder joint was evident. Small nodular lesions (round or irregular in shape, firm and gray, and 0.5 to 4 cm in diameter) were identified in the cervical muscles, lungs, kidneys, jejunal mesentery, and liver. The left eye was enlarged and congested; the globe appeared to be under pressure. Thickening of the optic nerve and edema of the posterior area of the affected globe were also observed. An irregular, well-encapsulated gray-white mass (1.6 × 1.2 × 0.8 cm) was identified within the vitreous chamber of the globe, attached to the optic disk. On cross section, this mass appeared to be extensively ossified.
Photographs of the left forelimb (A) and eyes (B through E) of a 14-year-old cat that was evaluated because of progressive swelling over the proximal portion of the left humerus and severe lameness both of 2 months’ duration. The cat was euthanized because of the poor clinical prognosis. A—Notice the gray-white, well-delimited, and lobular ovoid mass that extends from the proximal to middle portions of the humerus. Multiple and coalescing white calcified foci (arrows) and adjacent muscle atrophy are also present. Bar = 1 cm. B—Compared with the right eye (on right in panels B through D), the left eye is abnormally large, with hyperemia and edema of the sclera and the presence of glaucoma. C—On the posterior aspect of the left globe, enlargement of the optic nerve and edema of adjacent tissue (arrow) are evident. Bar = 1 cm. D—On cross section of the left globe, a white-gray, well-encapsulated, and multinodular mass (arrow) that is closely attached to the optic disk is visible Bar = 1 cm. E—On cross section of the ocular tumor, the mass appears white-gray with an extensively ossified area (asterisks). The arrow indicates the site of the optic disk. Bar = 1 cm.
Citation: Journal of the American Veterinary Medical Association 245, 10; 10.2460/javma.245.10.1103
Photographs of the left forelimb (A) and eyes (B through E) of a 14-year-old cat that was evaluated because of progressive swelling over the proximal portion of the left humerus and severe lameness both of 2 months’ duration. The cat was euthanized because of the poor clinical prognosis. A—Notice the gray-white, well-delimited, and lobular ovoid mass that extends from the proximal to middle portions of the humerus. Multiple and coalescing white calcified foci (arrows) and adjacent muscle atrophy are also present. Bar = 1 cm. B—Compared with the right eye (on right in panels B through D), the left eye is abnormally large, with hyperemia and edema of the sclera and the presence of glaucoma. C—On the posterior aspect of the left globe, enlargement of the optic nerve and edema of adjacent tissue (arrow) are evident. Bar = 1 cm. D—On cross section of the left globe, a white-gray, well-encapsulated, and multinodular mass (arrow) that is closely attached to the optic disk is visible Bar = 1 cm. E—On cross section of the ocular tumor, the mass appears white-gray with an extensively ossified area (asterisks). The arrow indicates the site of the optic disk. Bar = 1 cm.
Citation: Journal of the American Veterinary Medical Association 245, 10; 10.2460/javma.245.10.1103
Photographs of the left forelimb (A) and eyes (B through E) of a 14-year-old cat that was evaluated because of progressive swelling over the proximal portion of the left humerus and severe lameness both of 2 months’ duration. The cat was euthanized because of the poor clinical prognosis. A—Notice the gray-white, well-delimited, and lobular ovoid mass that extends from the proximal to middle portions of the humerus. Multiple and coalescing white calcified foci (arrows) and adjacent muscle atrophy are also present. Bar = 1 cm. B—Compared with the right eye (on right in panels B through D), the left eye is abnormally large, with hyperemia and edema of the sclera and the presence of glaucoma. C—On the posterior aspect of the left globe, enlargement of the optic nerve and edema of adjacent tissue (arrow) are evident. Bar = 1 cm. D—On cross section of the left globe, a white-gray, well-encapsulated, and multinodular mass (arrow) that is closely attached to the optic disk is visible Bar = 1 cm. E—On cross section of the ocular tumor, the mass appears white-gray with an extensively ossified area (asterisks). The arrow indicates the site of the optic disk. Bar = 1 cm.
Citation: Journal of the American Veterinary Medical Association 245, 10; 10.2460/javma.245.10.1103
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Cytologic and Histopathologic Findings
Multiple impression smears from the bone mass were stained with May-Grunwald Giemsa staina for cytologic examination. The smears were highly cellular, and those cells were spindloid to polygonal in shape. The cells were deep blue and had large, round to oval, eccentrically located nuclei with coarse granular chromatin and multiple prominent nucleoli. Multiple mitotic figures were identified. A variable amount of amorphous to fibrillar pink matrix (osteoid) was present between the cells, and low numbers of neutrophils and macrophages were also identified.
Several samples of the humeral mass and the pulmonary, renal, cervical muscle, mesenteric, and ocular nodules were fixed in phosphate-buffered 10% formalin for 24 hours and embedded in paraffin wax. Four-micrometer-thick sections were stained with H&E stain. Histologic evaluation of the lesions was performed according to published criteria.1 Histologically, the bone tumor was characterized by a multinodular growth pattern with local invasion and destruction of resident bone. The neoplastic cells were oval, spindle-shaped, or polygonal and had eosinophilic cytoplasm, large vesiculated nuclei, and at least 1 prominent nucleolus. There were 0 to 2 mitotic figures/hpf (40X). Multiple, widely separated islands of eosinophilic osteoid matrix containing malignant neoplastic cells were identified (Figure 2), as were small chondroblastic and fibroblastic areas and foci of necrosis. Mineralization and neoplastic bone formation were evident in both the bone mass and visceral lesions. Microscopic examination of the mass from the globe revealed cellular areas intermixed with areas of dense fibrillar matrix containing lower numbers of cells. In some areas, osteoblast-like cells were embedded in an eosinophilic osteoid matrix containing large, irregular, and basophilic foci of ossification. The neoplastic cells were also identified in blood capillaries adjacent to the optic nerve. There was no extension of the neoplasm to the periocular tissues.
Photomicrographs of sections of the primary and metastatic osteosarcoma tissues obtained from the cat in Figure 1. A—Section of the bone tumor. Notice a proliferation of neoplastic osteoblasts with marked osteoid production. A small mineralized basophilic area (top left) is present within the neoplastic mass. H&E stain; bar = 50 μm. B—Section of the ocular mass. The nodular mass is composed of malignant osteoblasts, osteoid matrix, and large basophilic ossified areas. H&E stain; bar = 200 μm. Inset—The neoplastic osteoblasts are mixed with eosinophilic fibrillar osteoid matrix. H&E stain; bar = 20 μm. C—Another section of the ocular mass. The cytoplasm of the neoplastic cells is positive for bone morphogenetic protein (BMP) 2 and BMP4. Immunohistochemical staining for BMP2 and BMP4 (streptavidin-biotin-peroxidase method) with Mayer's hematoxylin counterstaining; bar = 50 μm. D—Another section of the ocular mass. Several BPM2- and BMP4-immunostained neoplastic cells are present within capillaries of the vascular tunic of the choroid. Immunohistochemical staining for BMPs 2 and 4 (streptavidin-biotin-peroxidase method) with Mayer's hematoxylin counterstaining; bar = 20 μm
Citation: Journal of the American Veterinary Medical Association 245, 10; 10.2460/javma.245.10.1103
Photomicrographs of sections of the primary and metastatic osteosarcoma tissues obtained from the cat in Figure 1. A—Section of the bone tumor. Notice a proliferation of neoplastic osteoblasts with marked osteoid production. A small mineralized basophilic area (top left) is present within the neoplastic mass. H&E stain; bar = 50 μm. B—Section of the ocular mass. The nodular mass is composed of malignant osteoblasts, osteoid matrix, and large basophilic ossified areas. H&E stain; bar = 200 μm. Inset—The neoplastic osteoblasts are mixed with eosinophilic fibrillar osteoid matrix. H&E stain; bar = 20 μm. C—Another section of the ocular mass. The cytoplasm of the neoplastic cells is positive for bone morphogenetic protein (BMP) 2 and BMP4. Immunohistochemical staining for BMP2 and BMP4 (streptavidin-biotin-peroxidase method) with Mayer's hematoxylin counterstaining; bar = 50 μm. D—Another section of the ocular mass. Several BPM2- and BMP4-immunostained neoplastic cells are present within capillaries of the vascular tunic of the choroid. Immunohistochemical staining for BMPs 2 and 4 (streptavidin-biotin-peroxidase method) with Mayer's hematoxylin counterstaining; bar = 20 μm
Citation: Journal of the American Veterinary Medical Association 245, 10; 10.2460/javma.245.10.1103
Photomicrographs of sections of the primary and metastatic osteosarcoma tissues obtained from the cat in Figure 1. A—Section of the bone tumor. Notice a proliferation of neoplastic osteoblasts with marked osteoid production. A small mineralized basophilic area (top left) is present within the neoplastic mass. H&E stain; bar = 50 μm. B—Section of the ocular mass. The nodular mass is composed of malignant osteoblasts, osteoid matrix, and large basophilic ossified areas. H&E stain; bar = 200 μm. Inset—The neoplastic osteoblasts are mixed with eosinophilic fibrillar osteoid matrix. H&E stain; bar = 20 μm. C—Another section of the ocular mass. The cytoplasm of the neoplastic cells is positive for bone morphogenetic protein (BMP) 2 and BMP4. Immunohistochemical staining for BMP2 and BMP4 (streptavidin-biotin-peroxidase method) with Mayer's hematoxylin counterstaining; bar = 50 μm. D—Another section of the ocular mass. Several BPM2- and BMP4-immunostained neoplastic cells are present within capillaries of the vascular tunic of the choroid. Immunohistochemical staining for BMPs 2 and 4 (streptavidin-biotin-peroxidase method) with Mayer's hematoxylin counterstaining; bar = 20 μm
Citation: Journal of the American Veterinary Medical Association 245, 10; 10.2460/javma.245.10.1103
Immunohistochemical analysis of both the osseous and ocular neoplasms revealed that the cytoplasm of malignant cells had strong immunopositivity for vimentin (clone V9),b bone morphogenetic protein (BMP) 2, and BMP4 (clone H51c; Figure 2). Moreover, several neoplastic cells that were immunopositive for both BMP2 and BMP4 were identified within capillaries of the vascular tunic of the choroid. The neoplastic cells were negative for α-actin (clone HHF35),b polyclonal CD3,b cytokeratin (clone AE1/AE3),d and polyclonal S100 protein.b The cytoplasm of apparently normal osteoblasts within the bone was immunopositive only for vimentin, BMP2, and BMP4.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: productive osteoblastic osteosarcoma of the left humerus with unilateral eye, cervical muscle, pulmonary, renal, jejunal mesentery, and liver metastases.
Case summary: appendicular osteosarcoma with ocular metastasis in a cat.
Comments
Osteosarcomas are primary malignant bone tumors characterized by the production of osteoid and bone by neoplastic osteoblasts.1 Osteosarcoma is the most common malignant bone tumor in cats, representing approximately 70% to 80% of malignant primary bone tumors, and usually involves the appendicular skeleton.2 Extraskeletal sites of primary osteosarcoma, including subcutaneous tissue,3 mammary glands,2 and eyes,2,4 have been identified in cats. In cats, osteosarcoma develops slowly and metastasizes by a hematogenous route, usually to the lungs.5 Compared with dogs, in which the rate of metastasis is higher, metastasis is less common in cats.6 Metastatic orbital osteosarcoma is a rare condition and has been only described for dogs7 and humans.8
A definitive diagnosis of osteosarcoma is based on the production of osteoid by neoplastic mesenchymal cells.1 Histologically, the most frequent types of osteosarcoma are osteoblastic, chondroblastic, and fibroblastic.1 Giant cell osteosarcoma is a variant that is uncommon in veterinary species, although there is 1 report9 of a cat with giant cell osteosarcoma of the calvarium.
In the case described in the present report, the primary tumor was located in the left humerus with metastases to the left eye, cervical muscles, lungs, kidneys, jejunal mesentery, and liver. The masses were composed of pleomorphic neoplastic cells with eccentric nuclei and a moderate to abundant amount of cytoplasm. These cells were accompanied by variable amounts of osteoid matrix. On the basis of their morphological characteristics, the proliferating cells were interpreted to be osteoblasts. Because there are no lymphatic vessels in the retrobulbar area, metastatic tumors primarily reach the orbit via a hematogenous route.8 In the cat of the present report, the presence of neoplastic cells within capillaries in an area adjacent to the optic nerve supported the conclusion of tumor metastasis to the globe. Although, for osteosarcomas, the most frequent sites of metastases are the lungs and kidneys, additional sites including cervical muscles, liver, and mesentery also were identified in the present case.
Proteins such as BMPs are expressed by osteosarcoma cells and are sometimes used as prognostic indicators. The BMP subtypes 2 through 9 are the best characterized BMPs.10 Positive immunohistochemical reactions for vimentin, BMP2, and BMP4, along with AE1/AE3 immunonegativity, suggest a mesenchymal origin with osteoblastic differentiation of a tumor. With regard to the globe, primary tumors, such as melanomas, iridociliary epithelial tumors, and ocular sarcomas, develop more frequently than do metastatic neoplasms.11 In a recent study,12 orbital myofibroblastic sarcomas in 10 cats that underwent testing were positive for vimentin, S100 protein, and smooth muscle actin. Primary and metastatic melanocytic and myofibroblastic tumors were ruled out in the case described in the present report because the neoplastic cells were negative for S100 protein and smooth muscle actin. Feline primary ocular sarcoma (posttraumatic sarcoma) is a high-grade spindle cell tumor that grows as a distinctly perilenticular mass by means of fibroblastic metaplasia and hyperplasia of lens epithelial cells.11 For the cat of this report, diagnosis of a primary ocular sarcoma was ruled out on the basis of the ocular mass's location and marked production of osteoid and the negative reaction of the neoplastic cells after immunostaining for cytokeratin.
Any neoplasm likely to metastasize can potentially metastasize to the globe.11 In cats, the most prevalent metastatic tumor of the ocular globe is malignant lymphoma.11 Lymphoma commonly involves the anterior uvea at a late stage of generalized malignancy.11 In the cat of the present report, T-cell lymphoma was ruled out on the basis of cytologic and histologic features of the tissue samples examined and negative results of immunostaining of the neoplastic cells for CD3.
To our knowledge, this is the first description of ocular metastasis of an appendicular osteoblastic osteosarcoma in a cat. The histologic appearance of the primary osteosarcoma and the pattern of immunohistochemical expression in the primary tumor and the metastatic lesions both were useful in making the diagnosis and in differentiating metastatic osteosarcoma from other primary and metastatic ocular tumors.
Dia-Quick Panoptic, Reagent Ltd, Budapest, Hungary.
Dako Denmark A/S, Glostrup, Denmark.
Santa Cruz Biotechnology Inc, Heidelberg, Germany.
Invitrogen Corp, Camarillo, Calif.
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