BONE SCINTIGRAPHY FOR METASTASIS DETECTION IN CANINE OSTEOSARCOMA

The purpose of this study was to assess the usefulness of serial bone scintigraphy in the detection of skeletal and extraskeletal metastases in dogs with appendicular osteosarcoma. Twenty-six dogs with primary, appendicular osteosarcoma were entered into a limb-sparing protocol. Bone scintigraphy was performed upon presentation, after neoadjuvant therapy but prior to surgery and at selective intervals after limb-sparing surgery to evaluate for the presence of metastasis. Thoracic radiographs, and radiographs of other sites, were also made at the time of each bone scan. All dogs had a complete necropsy. No dog had bone or lung metastases detected prior to treatment. The bone scans, medical records, and radiographs of each dog were reviewed retrospectively. All but one dog developed metastatic disease. Bone metastatic sites were confirmed at necropsy in 12 of the 26 dogs. Seven of these 12 dogs had bone metastatic sites which were not producing clinical signs, i.e. an occult metastasis. In five of the seven dogs, the occult site was the first metastatic site detected. Extraskeletal metastases were identified scintigraphically in six of the 26 dogs, but these were clinically apparent prior to bone scintigraphy in each dog. Suspected malignant scintigraphic lesions were proven benign in six dogs. In five dogs with malignant bone lesions at necropsy the last bone scan prior to euthanasia was normal. The time interval between scintigraphy and necropsy was variable in these five dogs. All dogs without bone metastases at necropsy had normal bone scans. This study validates the usefulness of bone scintigraphy for detection of occult bone metastasis and improved ability for tumor staging in dogs with appendicular osteosarcoma.     

Intermandibular malignant mesenchymoma in a crossbreed dog

A 12-year-old German shepherd crossbreed dog was presented with a submandibular mass that was initially diagnosed as myxosarcoma on incisional biopsy. Chest radiographs were taken for staging, and magnetic resonance imaging was performed to assess the feasibility of cytoreductive surgery before adjuvant radiotherapy. The dog underwent debulking surgery, and histology permitted reclassification of the tumour as a malignant mesenchymoma (with myxosarcomatous and osteosarcomatous differentiation). The dog was subsequently treated with four fractions of radiotherapy given at seven-day intervals and three doses of carboplatin. The dog remained stable following therapy until its condition acutely deteriorated, and it was euthanased 153 days after surgery. On postmortem examination, there were no signs of local tumour recurrence, but metastases were observed both in the thorax and in the abdomen.     

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.     

SCINTIGRAPHIC DETECTION OF SUBCUTANEOUS METASTASIS IN A DOG WITH APPENDICULAR OSTEOSARCOMA

This report describes the detection of subclinical soft tissue metastasis of an appendicular osteosarcoma in a dog using bone scintigraphy. A 7-year-old spayed female Rottweiler was presented with a biopsy confirmed diagnosis of osteosarcoma. Initial radiographs revealed an aggressive bone lesion of the left distal radius. At presentation, there was no clinical or radiographic evidence of metastasis; however, a nuclear bone scan showed the primary bone lesion of the distal left radius and numerous soft tissue lesions consistent with diffuse soft tissue metastases. A left foreleg amputation was performed and cisplatin chemotherapy was given post-operatively. A second bone scan performed one month following initial presentation showed progression in size and number of soft tissue masses. Many of the lesions had become apparent on physical exam and survey radiographs. Excisional biopsy was performed on one of the soft tissue masses and a diagnosis of metastatic osteosarcoma was made. The dog was euthanized 2 months after initial presentation at the owners request due to deterioration of the animals physical condition.     

Mandibular ossifying fibroma in a dog

An aged mongrel dog was admitted for hemimandibulectomy as treatment for a mandibular mass that had been diagnosed as osteosarcoma. The fibro-osseous mass that surrounded the first molar tooth and replaced alveolar and cortical bone was reclassified as ossifying fibroma on the basis of anatomic location and histologic features. The tumor was composed of isomorphic fusiform cells with few mitotic figures. Tumoral stroma contained trabeculae of woven bone that were bordered by a single layer of osteoblasts. Excision was deemed complete with no evidence of extension or metastasis by computed tomography of the skull or thoracic and abdominal radiography. The dog was reportedly healthy 6 months after initial presentation. Though far less common than osteosarcoma as a primary canine bone tumor, ossifying fibroma should be included in the differential diagnosis for fibro-osseous proliferations, especially those of the jaw. Although benign, en bloc excision may be necessary for surgical cure.     

A dog with osteosarcoma which metastasized to the eye months before metastasis to other organs

A 9-year-old male Shih Tzu with osteosarcoma had a forelimb amputation and underwent chemotherapy. During chemotherapy, the right eye was enucleated due to refractory glaucoma, and was diagnosed as anterior uveal malignant melanoma. The dog lived for 4 months after the enucleation without treatment. After the dog died, the mass in the eye was re-evaluated immunohistochemically, and it was diagnosed as metastasis of appendicular osteosarcoma. Metastasis of appendicular osteosarcoma to the anterior chamber is quite rare, and the clinical course which showed clinically detectable metastases to the eye before systemic multi-organ metastases was quite unique.     

Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.     

Hepatic malignant mesenchymoma in a dog

Hepatic malignant mesenchymoma was diagnosed in a dog with a history of gradual abdominal distension of 2 months' duration. The tumor was polycystic and attached to the caudal border of the left lateral liver lobe. The dog was euthanatized 16 weeks after surgical excision. Necropsy revealed tumor metastasis throughout the liver.     

Outcome of a dog with urinary bladder osteosarcoma treated with a total cystectomy and ureterocutaneostomy

A 10-year-old, neutered female, French bulldog was presented with a history of dysuria, hematuria, stranguria, and pollakiuria. Diagnostic tests revealed a large mass at the neck of the bladder without any evidence of metastatic disease. Total cystectomy with bilateral cutaneous ureterostomy creation was elected. Histopathology of the bladder mass revealed extraskeletal osteosarcoma, which was resected completely. Neither recurrence nor metastasis had been detected as of 65 months after surgery. Extraskeletal osteosarcomas are typically malignant and carry a poor prognosis. This is the first report of bladder osteosarcoma in a dog treated by total cystectomy and ureterocutaneostomy with excellent long-term control.     

Primary and secondary bone tumours in the dog

During a 14-year period (January 1962 to December 1975), 394 primary and secondary tumours or tumour-like lesions affecting bones were diagnosed in the dog. The most frequently occurring tumour was osteosarcoma (183, 46.5%), followed by chondrosarcoma (forty-four, 11.2%), squamous cell carcinoma (thirty-nine, 10%), fibrosarcoma (thirty-one, 7.8%), multiple myeloma (fourteen, 3.6%), haemangiosarcoma (fourteen, 3.6%), malignant melanoma (thirteen, 3.3%), synovioma (nine, 2.3%), lymphosarcoma (eight, 2.0%), cartilage analogue of fibromatosis (seven, 1.8%), adaman-tinoma (five, 1.3%), osteocartilaginous exostosis, ossifying fibroma, rhabdomyosarcoma (four each), polyostotic cyst, haemangiomatosis (three each), odontoma, tumoral calcinosis (two each), and osteoma, chondroma, desmoid fibromatosis, and malignant mesenchymoma (one each).
Of these, desmoid fibromatosis, malignant mesenchymoma, and haemangiomatosis have not been previously reported in the dog.     

High-grade surface osteosarcoma in a dog

A case of a high-grade surface osteosarcoma in the thoracic limb of a dog is reported. Radiographically, there was no bone involvement but there was increased soft tissue opacity. An aggressive osteosarcoma was diagnosed on the basis of early metastatic disease and histopathological examination. Previously reported surface osteosarcomas in the dog have been periosteal and parosteal osteosarcomas which are generally considered to have a low to intermediate biological activity. The tumour described here had radiographical, gross pathological, histopathological and biological features consistent with human high-grade surface osteosarcoma. The characteristics of surface osteosarcomas are briefly reviewed.     

Malignant histiocytosis in a Bernese mountain dog presenting as a mandibular mass.

A Bernese mountain dog was evaluated because of a gingival mass, multiple abdominal masses, and a pulmonary mass. Malignant histiocytosis was diagnosed based on cytological examination of splenic and bone marrow aspirates and histological examination of a bone marrow biopsy and the gingival mass. The case demonstrates that malignant histiocytosis is difficult to diagnose due to the variety of histiocytic disorders.     

The tyrosine kinase inhibitor sorafenib decreases cell number and induces apoptosis in a canine osteosarcoma cell line

Canine osteosarcoma, an aggressive cancer with early distant metastasis, shows still despite good chemotherapy protocols poor long term survival. The aim of our study was to determine whether sorafenib, a novel multikinase inhibitor, has any effect on D-17 canine osteosarcoma cells.A cell proliferation kit was used for detecting surviving cells after treatment for 72 h with sorafenib or carboplatin or their combination. A significant decrease of neoplastic cells was observed after incubation with 0.5-16 μM sorafenib or with 80-640 μM carboplatin. Using immunocytochemistry for activated caspase 3 to evaluate apoptosis, we found significantly more positive cells in the sorafenib treated groups. Paradoxically, expression of the nuclear proliferation marker Ki-67 was also significantly higher in sorafenib treated cells. The drug sorafenib showed potent antitumour activity against D-17 canine osteosarcoma cells in vitro, suggesting a potential as a therapeutic tool in the treatment of bone cancer in dogs.     

OSTEOSARCOMA OF THE PATELLA WITH PULMONARY METASTASES IN A DOG

A 6-year-old neutered male Rottweiler was examined for a progressive right pelvic limb lameness. In radiographs of the right stifle, there was an osteolytic lesion with irregular new bone formation along the cranial aspect of the patella consistent with an aggressive bone lesion. In thoracic radiographs, there were multiple soft tissue nodular opacities throughout the lung fields, consistent with pulmonary metastases. Microscopically, fine needle aspirate samples from the right patella contained pleomorphic spindle cells with cytologic features of osteosarcoma. The presence of pulmonary metastases at the time of initial diagnosis in the dog described herein suggests that osteosarcoma of the patella has the potential for similar aggressive biologic behavior as that seen in dogs with appendicular osteosarcoma.     

Zoledronic acid for the treatment of appendicular osteosarcoma in a dog

A 10-year-old male intact Corso dog was referred for lameness and for a large neoplasm affecting the right foreleg. Physical examination of the patient revealed a 5 × 5 × 3 cm mass in the distal right foreleg. Histopathology was consistent with a diagnosis of appendicular osteosarcoma. The staging process found no evidence of metastasis. Because of the large size of the patient, the owners elected to treat their dog with antiresorptive therapy. The patient was treated with an infusion of zoledronic acid every 28 days. The tumour remained stable for 16 months and the lameness of the dog greatly improved. At that time, the patient returned for evaluation of a large rapidly growing prescapular mass. Biopsy confirmed lymph node metastasis and the dog was euthanased. Zoledronic acid showed remarkable palliation in our patient and possibly anti-tumour action and warrants further investigation.     

Primary jejunal osteosarcoma associated with a surgical sponge in a dog

Primary jejunal osteosarcoma was diagnosed in association with a surgical sponge in a dog. The tumor was biologically aggressive, resulting in widespread metastasis throughout the abdomen within 2 months of surgical resection. Microscopic examination of the resected osteosarcoma revealed strands of gauze material throughout the tumor mass. It was theorized that the presence of a sponge foreign body may have resulted in malignant transformation of adjacent tissues similar to what has been reported to occur after internal fixation of some long-bone fractures.     

Extraskeletal osteosarcoma in a cat.

A 7-year-old spayed female domestic shorthair cat was referred for evaluation of a localized growing mass on the left flank. Cytologic and histologic findings suggested that the mass was an extraskeletal osteosarcoma. Radiography failed to reveal any association between the lesion and the axial or appendicular skeleton. Because of the large size of the tumor, the cat was treated with carboplatin prior to and after surgery (hemipelvectomy) to ensure that surgical margins were free of neoplastic cells and to prevent systemic dissemination of malignant cells. The tumor has not recurred during a 2-year follow-up period.     

Primary sarcoma of the ribs in a large, mixed breed dog

A 9-year-old, 30-kg, neutered male, mixed breed dog was referred for en bloc resection of a tentatively diagnosed costal chondrosarcoma. Light microscopic examination of the excised mass confirmed osteosarcoma. Adjuvant chemotherapy with 4 treatments with carboplatin was initiated. There have been no signs of metastases 5 months postsurgery.     

Bone scintigraphy in the initial evaluation of dogs with primary bone tumors

Bone scintigraphy was performed as part of an initial diagnostic evaluation of 70 dogs admitted with primary bone tumors during a 2-year period. Tumors involved major long bones of the appendicular skeleton and included 62 osteosarcomas, 6 fibrosarcomas, and 2 chondrosarcomas. All dogs were free of radiographically detectable pulmonary metastases. Bone scintigraphy was not of value in distinguishing among various types of primary tumors. One dog with an ulnar chondrosarcoma had a scintigraphically detectable occult osseous metastasis or synchronous primary tumor, and 1 dog with osteosarcoma had a scintigraphically detectable lymph node metastasis. Pulmonary metastases were not detected scintigraphically. Of the 70 dogs, 44.3% had areas of increased isotope uptake associated with nonneoplastic disease processes.     

Long-term complete chimerism and stable hematopoiesis in beagles after fetal liver hematopoietic stem cell transplantation

Karyotype analysis of bone marrow cells was performed from 6 Beagles that had received sex-mismatched fetal liver hematopoietic stem cell grafts 2.4 to 6.5 years earlier. Two dogs received dog leukocyte antigen-matched fetal liver cells and 4 received dog leukocyte antigen-mismatched cells. In each dog, all 25 evaluated metaphase spreads were of donor genotype. All dogs had normal hemograms and repopulation of bone marrow and no dog developed graft-vs-host disease.