Right ventricular rupture after lateral thoracotomy for removal of rib-associated telangiectatic osteosarcoma in a dog

Objective – To describe a case of a focal right ventricular rupture following removal of a rib-associated telangiectatic osteosarcoma (TOS) in a dog.
Case Summary – A 2-year-old spayed female mixed-breed dog, weighing 20 kg, was presented in compensated hypovolemic shock due to active bleeding into the thoracic cavity. The dog was stabilized with appropriate fluid administration. Subsequent computed tomographic examination revealed a large mineralized mass originating from the body of a rib and displacing the heart. Two days after surgical removal of this mass, focal right ventricular rupture occurred and the dog died. The mass was later identified as a TOS.
New or Unique Information Provided – Although hemothorax secondary to TOS has been described previously, this report describes for the first time, spontaneous focal right ventricular rupture as a rare complication of thoracotomy and rib resection for the removal of a rib-associated, intrathoracic TOS.     

Cutaneous metastasis of primary appendicular osteosarcoma in a dog

A 6-year-old, neutered male Rottweiler was presented to the University of Illinois Veterinary Teaching Hospital because of a lytic bone lesion involving the distal portion of the right radius and possible pulmonary metastases on thoracic radiographs. Results of serum biochemical analysis were unremarkable. Aspiration and cytologic examination of the bone lesion indicated likely sarcoma with reactive bone. Cutaneous masses were found on the left thigh, interscapular region, and dorsal lumbar region, 4 weeks after initial presentation. Neoplastic spindle cells were found in aspirates from 2 of the masses. The neoplastic cells stained positive for alkaline phosphatase activity using cytochemistry. Re-evaluation of serum biochemical values at this time revealed a marked increase in alkaline phosphatase activity (413 U/L, reference interval 12-110 U/L) compared with the initial value (26 U/L). Due to progressive disease, the dog was euthanized and a necropsy was performed. Histologic findings included primary osteosarcoma of the distal portion of the right radius, with metastases in the lungs, spleen, left fourth and fifth ribs, soft tissue of the right medial thigh, and T1-T3/interscapular region. Cutaneous metastasis of primary appendicular osteosarcoma has been reported rarely in animals and humans. Increased serum alkaline phosphatase activity may be a potential indicator of poor prognosis for this neoplasm.     

Hemothorax associated with telangiectatic osteosarcoma in a dog

Hemothorax in a dog was attributed to bleeding from an intrathoracic mass attached to the sixth through the tenth ribs. The mass contained numerous cavernous, blood-filled spaces as well as bands of osteoid and occasional foci of osseous tissue. The diagnosis was telangiectatic osteosarcoma. Telangiectatic osteosarcoma is an uncommon variant of osteosarcoma. Cavernous, blood-filled spaces and paucity of bone are important histologic features. Metastasis was described in one of the seven telangiectatic osteosarcomas reported in dogs, and none was found in this case.     

Primary ocular osteosarcoma in a dog

An adult male Rottweiler presented to the veterinary medical teaching hospital at Purdue University with a 1-month history of hyphema. On physical examination conjunctivitis, episcleral hyperemia, corneal edema, hyphema, mild glaucoma and loss of vision were observed in the left eye. No other abnormalities were found. The left globe was surgically removed because of the high likelihood of neoplasia and it was fixed in 10% buffered formalin and submitted for pathology. A histologic diagnosis of primary osteosarcoma of the eye was made. Radiographic evaluation did not reveal any evidence of other tumors or pulmonary metastasis. This is the fourth canine case of primary intraocular osteosarcoma to be documented.     

Limb-sparing surgery in a dog with osteosarcoma of the proximal femur

OBJECTIVE: To report successful limb-sparing surgery in a dog with a proximal femoral osteosarcoma (OSA) using a composite allograft-prosthetic technique. STUDY DESIGN: Case report. ANIMAL: Client-owned dog. METHODS: A stage IIB OSA of the proximal aspect of the femur was resected in accordance with oncologic and limb-sparing principles. The osseous defect was reconstructed with a proximal femoral allograft and cemented, long-stemmed femoral prosthesis. Soft tissue reconstruction was achieved by suturing host tendons to their respective allogeneic tendons on the allograft. Coxofemoral joint function was preserved using standard total hip arthroplasty techniques. RESULTS: Limb-sparing surgery of the proximal aspect of the femur using a composite allograft-prosthetic technique resulted in excellent limb function. Postoperative complications included aseptic loosening of the femoral composite graft and allograft nonunion, which required revision, traumatic implant luxation, and local tumor recurrence. Limb function was excellent after surgical stabilization of the allograft nonunion but deteriorated after implant luxation 270 days postlimb-sparing surgery. Pulmonary and skeletal metastases were diagnosed and local tumor recurrence suspected 596 and 650 days postoperatively, respectively. The dog was euthanatized 688 days after limb-sparing surgery as a result of progressive local and metastatic disease. CONCLUSIONS AND CLINICAL RELEVANCE: Limb-sparing surgery for dogs with primary bone tumors of the proximal aspect of the femur is feasible with good functional results.     

Primary mesenteric root osteosarcoma in a dog

Abstract: A 10‐year‐old spayed female Boxer‐mix was presented with a history of several weeks of soft stools, straining to defecate, inappetance, and lethargy and several days of hematochezia, melena, and dyschezia. Physical examination findings included mild tachycardia and tense cranial abdomen. CBC results indicated moderate mature neutrophilia. Ultrasonographic examination of the abdomen revealed a large mass with complex echogenicity in the cranial abdomen, likely associated with the intestines. Cytologic examination of a fine‐needle aspirate revealed a population of round, stellate, and spindle‐shaped cells arranged individually and in aggregates with occasional cells embedded in an eosinophilic extracellular matrix. The cytologic interpretation was malignant mesenchymal neoplasm with osteosarcoma being the primary differential. Surgical exploration of the abdomen revealed a 10‐cm‐diameter mass located at the intestinal mesenteric root. The mass occluded blood flow to portions of the gastrointestinal tract. The dog was euthanized due to the nonresectable nature of the tumor. Histopathologic examination revealed an expansile poorly demarcated mesenchymal neoplasm composed predominantly of spindloid and pyriform cells, occasionally embedded in a matrix compatible with osteoid. The diagnosis was extraskeletal osteosarcoma of the intestinal mesenteric root, only rarely reported in dogs.     

Oral and maxillofacial osteosarcoma in dogs: a review

Osteosarcoma in dogs is a heterogeneous disease entity with regard to its histologic, clinical and biologic behaviour. Differences in behaviour are associated with tumour location. Oral and maxillofacial osteosarcomas are typically reported as a component of the broader classifications of axial osteosarcoma or osteosarcoma of flat bones to differentiate them from appendicular osteosarcoma. Similar to human oral and maxillofacial osteosarcoma, in dogs, these also appear to have less aggressive behaviour than appendicular osteosarcoma. Ideally, local control is achieved with wide surgical resection that results in tumour‐free margins. Failure of local control is the most common contributor to poor prognosis. Chemotherapy and radiation treatment are reported to have variable outcomes. The aim of this article is to review the literature on oral and maxillofacial osteosarcoma in dogs in comparison to appendicular and axial osteosarcoma. Similarities and differences between oral and maxillofacial osteosarcoma in humans are addressed.     

Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach

A 10‐year‐old, female spayed mixed‐breed or cross‐bred dog was referred to the Small Animal Teaching Hospital of the University of Liverpool due to tachypnea, dyspnea, and pleural effusion not responding to diuretics and antibiotics. The chest was drained and cytology of the pleural fluid was consistent with a modified transudate with presence of atypical cells initially attributed to mesothelial hyperplasia and dysplasia. Computed tomography detected, in addition to the bilateral pleural effusion, diffuse pleural thickening, multiple pleural and pulmonary nodules, and a mineralized and lytic mass in the left scapula. Imaging findings were suggestive of a primary bone tumor with intrathoracic metastasis. Cytology of the left scapular and pleural masses revealed a malignant neoplasm highly suggestive of osteosarcoma. The diagnosis was confirmed by demonstration of a positive cytochemical reaction for alkaline phosphatase on prestained cytology slides. This finding prompted review of the initial interpretation of the pleural effusion cytology. The presence of neoplastic osteoblasts in the thoracic fluid was identified by a combination of cytochemistry, cell pellet immunohistochemistry, and transmission electron microscopy findings. In this report, a multidisciplinary integrated diagnostic approach was used to diagnose and confirm a neoplastic pleural effusion due to osteosarcoma metastasis in a dog.     

Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells

The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.     

Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma

Efficacious therapies for measurable metastatic canine osteosarcoma (OSA) are generally lacking. Preliminary retrospective studies suggested that approximately 50% of dogs with measurable metastatic OSA experienced clinical benefit (objective response or clinically meaningful disease stabilisation) following toceranib (TOC) treatment. The purpose of this clinical trial was to prospectively evaluate the clinical outcome following TOC treatment in dogs with measurable pulmonary metastatic OSA. A secondary goal was to identify potential biomarkers of clinical benefit by measuring changes in plasma vascular endothelial growth factor (VEGF) and circulating regulatory T‐cell (Treg) percentage. Twenty‐two dogs with pulmonary metastasis from appendicular OSA having undergone previous amputation were treated prospectively with TOC. Adverse events (AEs) were common but predominantly low grade. Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable AEs. Of the patients evaluable for disease progression at week 8 (or earlier), 3/17 (17.6 %) had stable disease with the remainder having PD. The median progression‐free survival time for all patients was 57 days (range 7‐176 days) with a median overall survival time of 89 days (range 7‐574 days). Plasma VEGF concentrations were significantly elevated in patients after 4 weeks of TOC treatment, but no changes were observed in percentage of Treg in peripheral blood. Overall, the results of this clinical trial do not support the use of TOC as single agent therapy for canine metastatic OSA.     

Muscular and collagenous cerebellar choristoma in a dog

This report aims to describe the first case of muscular and collagenous choristoma in a dog. A 10-yr-old female mixed-breed dog presented with lateral recumbence, vocalization, positional vertical nystagmus, divergent strabismus, anisocoria, and status epilepticus. The clinical condition evolved to stupor and ultimately, death. Necropsy revealed a white mass causing an irregular increase in the volume of the cerebellar vermis. In histological analysis, a well circumscribed, unencapsulated mass was observed in the cerebellum, consisting of fibers of striated skeletal muscle and collagen fibers, mostly mineralized. Based on the histopathological and histochemical findings, a diagnosis of muscular and collagenous cerebellar choristoma was made.     

PAROSTEAL OSTEOSARCOMA OF THE CERVICAL VERTEBRA IN A DOG

A 12-year-old Maltese terrier was evaluated for progressive tetraparesis and neck pain. On radiographs, there was a periosteal reaction involving the fourth cervical vertebra. Myelographically, there was extradural compression of the spinal cord associated with the lesion. The dog was euthanized and necropsied. Histopathologic diagnosis was parosteal osteosarcoma of the vertebra.     

Development of a new canine osteosarcoma cell line

Establishing a canine osteosarcoma (OSA) cell line can be useful to develop in vivo and in vitro models of OSA. The goal of this study was to develop, characterize and authenticate a new canine OSA cell line and a clone. A cell line and a clone were developed with standard cell culture techniques from a naturally occurring OSA in a dog. The clonal cell line induced a tumour after injection in RAG 1‐deficient mouse. Histology was consistent with OSA. The original tumour from the dog and the tumour induced in the mouse were both reactive with vimentin and osteonectin (ON). The parent cell line and clonal cell line were reactive with ON, osteocalcin and alkaline phosphatase. Loss of heterozygosity was found in the same three microsatellite markers in the parent and clonal cell lines, and the tumour tissue grown in the mouse.     

Comparison of examination of thoracic radiographs and thoracic computed tomography in dogs with appendicular osteosarcoma

Appendicular osteosarcoma (OSA) is a highly metastatic tumour in dogs. The aim of the study was to compare thoracic radiographs with thoracic computed tomography (CT) in the staging of canine appendicular OSA. In all, 39 canine patients histologically diagnosed with OSA were reviewed in the retrospective study. All dogs underwent radiographic examination as well as CT examination of the thoracic cavity. Pulmonary nodules were detected radiographically in two cases (5%), whereas the CT imaging showed that pulmonary nodules were evident in 11 cases (28%, P = 0.024). There was an improved detection of small pulmonary nodules in the lung parenchyma with CT (P = 0.021). The number of nodules in CT examination had a significant negative influence on survival time (P = 0.005). However, whether nodules were present in CT or not did not influence overall survival (P = 0.368). CT examination was superior to thoracic radiography in the screening and detection of pulmonary nodules in dogs with OSA.     

Prostatic sarcomatoid carcinoma in a dog: cytologic and immunohistochemical findings

An 8-year-old neutered male Boxer was presented with tenesmus, hemorrhagic urethral discharge, and dysuria. Abdominal ultrasound and radiographic examinations revealed irregular prostatic enlargement. Laparotomy was performed and intraoperative cytology was done on imprint smears of a biopsy specimen obtained from a prostatic mass. The cytologic preparation was highly cellular and contained a predominant population of atypical, large, loosely cohesive spindle cells, with rare multinucleated cells and mitotic figures. The cytologic findings were consistent with undifferentiated sarcoma. At necropsy, a large cystic prostatic mass and numerous satellite nodules in the soft tissues around the pelvis were found. On histologic examination the tumor was composed primarily of bundles of neoplastic spindle cells. Rare pseudo-acinar structures and signet-ring cells also were observed. On immunohistochemical examination, the neoplastic cells co-expressed cytokeratin and vimentin. Based on histologic and immunohistochemical findings, the tumor was diagnosed as primary prostatic sarcomatoid carcinoma. This is a rare tumor in dogs, in which biphasic morphology of epithelial and mesenchymal cells can complicate the diagnosis, requiring immunochemical stains for confirmation.     

Cytologic and immunohistochemical characterization of a lung carcinoid in a dog

An 11-year-old neutered male Yorkshire Terrier was presented to the Haemaru Referral Animal Hospital with a history of unresponsive tracheal collapse and an incidental finding of a lung nodule in the left caudal lung lobe on radiography. Thorough physical examination and imaging studies revealed no other masses. Cytologic examination of C-arm mobile fluoroscopy-guided fine-needle aspirates revealed numerous free nuclei and a low number of small round cells with moderate to abundant pale basophilic cytoplasm. Some cells contained indistinct basophilic granules in their cytoplasm, and extracellular pink material was noted. A caudal lung lobectomy was performed, and histologic evaluation of the mass revealed round to polygonal cells with abundant eosinophilic granular cytoplasm and round nuclei with mild anisokaryosis and 0-3 mitotic figures per high-power field. Cells were arranged in packets separated by fine fibrovascular stroma, suggestive of a pulmonary neuroendocrine neoplasm, specifically a carcinoma/carcinoid. The cells were immunoreactive for chromogranin A and neuron-specific enolase, and negative for cytokeratin, synaptophysin, calcitonin, thyroglobulin, parathyroid hormone, CD79a, light lambda, and vimentin. With these findings the tumor was diagnosed as a primary lung carcinoid. Eleven months after resection, there was no evidence of tumor regrowth or metastasis. The absence of necrosis, few mitotic figures, minimal pleomorphism, and benign behavior of this tumor resembled those of a typical carcinoid in humans.     

Use of routine histopathology and factor VIII‐related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs

Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII‐related antigen/von Willebrand factor (FVIII‐RAg/vWF) is a well‐documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII‐RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII‐RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII‐RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA.     

A novel small molecule Met inhibitor, PF2362376, exhibits biological activity against osteosarcoma

The receptor tyrosine kinase Met is dysregulated in several human cancers including osteosarcoma (OSA) in which overexpression is a negative prognostic indicator and enforced Met expression in normal osteoblasts leads to genomic instability and malignant transformation. Met is also known to be inappropriately expressed in canine OSA tumour samples and cell lines. The purpose of this study was to evaluate the potential utility of an orally bioavailable small molecule Met inhibitor, PF2362376, against canine OSA cell lines as a prelude to future clinical work. PF2362376 inhibited phosphorylation of Met, Gab‐1, Erk and Akt, but not of Src or STAT3. Furthermore, PF2362376 inhibited proliferation of canine OSA cell lines and induced cell death at biologically achievable concentrations. Last, activities associated with Met signalling including migration, invasion, branching morphogenesis and colony formation in soft agar were blocked by PF2362376. These studies support the notion that Met is a relevant target for therapeutic intervention in OSA.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.