P‐62 Dermal and subcutaneous extraskeletal osteosarcomas in eight dogs,two cats,and one ferret

Osteosarcoma is a malignant mesenchymal neoplasm characterized by the formation of osteoid tissue. It is the most frequent primary bone tumour in dogs, accounting for nearly 80–85% of all reported long bone appendicular osteosarcomas. Conversely, in cats and other species, osteosarcoma is rare at any site. Extraskeletal osteosarcoma (EOS) is a malignant, osteoid‐producing neoplasm without primary periosteal or bone involvement. These tumours have been described less frequently and occur mainly in the mammary glands of female dogs. Case material was obtained from biopsy records of the Pathology Service at the Veterinary School, Universidad Nacional. The diagnosis of these tumours was based on the absence of clinical, radiological, or pathological evidence of primary bone or glandular involvement. Samples were processed for histopathological examination and stained with H&E. In two cases, immunohistochemistry was performed. Eleven cases were diagnosed with EOS located in two histological locations. The dermal group consisted of three female dogs (two Rottweillers and one Fila Brasileiro), one male German shepherd (mean age of dogs: 5.5 years), two female cats (mixed‐breed and Siamese) of 5 and 11 years of age, respectively, and one 4‐year‐old female ferret. The subcutaneous group consisted of four dogs, two female pit bull terriers and two male dogs (boxer and mixed‐breed), with a mean age of 5 years. The subcutaneous EOS tumours were more aggressive. Three dogs were euthanized due to lung metastasis and the remaining dog was lost to follow‐up. Funding: Self‐funded.     

Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008–2013

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non‐mammary and non‐thyroidal soft tissue and visceral EOS in dogs. Thirty‐three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0–458 days) versus median survival time of 13 days (range: 0–20 days)]. The use of surgery should be considered in the management of dogs with non‐mammary and non‐thyroidal soft tissue and visceral EOS.     

Primary and secondary bone tumours in the cat

Both primary and secondary bone tumours are rare in cats. Of the twenty-four cases of primary bone tumour, benign or malignant, in the cats of our study, the most common tumour was osteosarcoma (fifteen cats). The osteosarcomas tended to occur in aged female domestic short-hair cats; nine of the fifteen originated in the long bones of the extremities and three involved the skull. Four juxtacortical osteosarcomas, three chondro-sarcomas, and one example each of oesteoma and osteoid osteoma were found. The four juxtacortical osteosarcomas developed in relation to cranial bones, a location not recorded previously in cats.
Of the five tumour-like lesions of bone simulating primary tumours, three were aneurysmal bone cysts and two were fibrous dysplasias.
Of the twenty-nine cats with soft tissue tumours or tumour-like lesions involving bone, eleven had fibrosarcoma, eight had squamous cell carcinoma, three had lymphosarcoma, two had rhabdomyosarcoma, and one example of each was malignant melanoma, haemangiosarcoma, reticulum-cell sarcoma, meningioma and myositis ossificans.
Osteoid osteoma, fibrous dysplasia and myositis ossificans were not previously recorded in the cat.     

Nasal adenocarcinoma metastatic to bone in two dogs

Diagnosis of nasal adenocarcinoma was made in a 6-year-old 35-kg neutered Golden Retriever and a 6-year-old 8-kg spayed mixed-breed dog with chronic bilateral nasal discharge unresponsive to antibiotics. Treatment for the Golden Retriever consisted of bilateral rhinotomy, curettage, and postoperative fractionated 48-Gy orthovoltage irradiation. The mixed-breed dog was treated with cisplatin. After complete remission of the primary neoplasm, the dogs were reevaluated because of acute lameness. Radiography of the right stifle of the Golden Retriever revealed soft tissue swelling, extensive bony destruction of the distal femoral metaphysis and epiphysis, and pathologic fracture involving the medial condyle. Radiography of the left scapula of the mixed-breed dog revealed lysis of the glenoid cavity and subchondral scapular bone. Diagnosis of metastatic carcinoma was made in both dogs. With treatment improvements and longer survival time of affected dogs, sinonasal neoplasia may be observed to develop in similar life-threatening metastatic sites.     

The Immunotherapy of Canine Osteosarcoma: A Historical and Systematic Review

Osteosarcoma is a malignant mesenchymal neoplasm that accounts for the majority of primary bone tumors in dogs and shares biological and clinical similarities with osteosarcoma in humans. Despite dose intensification with conventional cytotoxic therapies, survival times for dogs and humans diagnosed with high‐grade osteosarcoma have not changed in the past 20 years, with the principal cause of mortality being the development of pulmonary metastases. Given the therapeutic plateau reached for delaying metastatic progression with cytotoxic agents, exploration of alterative adjuvant therapies for improving management of osteosarcoma micrometastases is clinically justified. Evidence suggests that osteosarcoma is an immunogenic tumor, and development of immunotherapies for the treatment of microscopic lung metastases might improve long‐term outcomes. In this review, the history and foundational knowledge of immune interactions to canine osteosarcoma are highlighted. In parallel, immunotherapeutic strategies that have been explored for the treatment of canine osteosarcoma are summarized. With a greater understanding and awareness for how the immune system might be redirected toward combating osteosarcoma metastases, the rational development of diverse immune strategies for managing osteosarcoma holds substantial promise for transforming the therapeutic landscape and improving disease management in both dogs and human beings.     

A Retrospective Study of Cavernous Sinus Syndrome in 4 Dogs and 8 Cats

Cavernous sinus syndrome (CSS) is characterized by deficits in more than one of the cranial nerves (CN) that traverse the cavernous sinus at the base of the cranial vault: CN III (oculomotor), IV (trochlear), VI (abducens), and the first two branches of CN V (trigeminal). Records from 4 dogs and 8 cats with CSS diagnosed over a 14-year period were reviewed. The most common clinical signs were ophthalmoparesis or ophthalmoplegia, mydriasis with no direct or consensual pupillary light reflexes, ptosis, decreased corneal sensation, and decreased retractor oculi reflex. All cats had initial signs referable to a left CSS lesion (one had bilateral CSS), whereas in all dogs the lesions were localized to the right cavernous sinus. Median ages at diagnosis were 9 and 10 years of age for dogs and cats, respectively. Cerebel lomedullary cisternae cerebrospinal fluid analysis in 6 animals was useful as a sensitivebut nonspecific diagnostic test of an intracranial inflammatory or neoplastic lesion. Magnetic resonance imaging scans provided a more definitive diagnostic test in all dogs, revealing a contrast-enhancing mass on T1 weighted scans in the region of the cavernous sinus. A definitive pathological diagnosis was obtained in 2 dogs: a primary intracranial neoplasm and a metastatic intracranial neoplasm. A definitive diagnosis was obtained in 6 cats: metastatic neoplasm (n =1), primary intracranial neoplasm (n = I), primary intracranial infectious disease (n = 2). and associated systemic infectious disease (n = 2). The prognosis associated with CSS in dogs and cats was considered guarded to poor. J Vet Intern Med 1996_;10:65–71. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

Expression of receptor activator of nuclear factor kappa-B ligand (RANKL) in neoplasms of dogs and cats

BACKGROUND: Receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis. HYPOTHESIS: Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology. ANIMALS: Forty-two dogs and 6 cats with spontaneously-occurring tumors involving bones or soft tissues were evaluated. METHODS: A polyclonal anti-human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor-bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology. RESULTS: Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x-ray absorptiometry. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism.     

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence*

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty‐six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.     

Diagnoses and clinical outcomes associated with surgically amputated feline digits submitted to multiple veterinary diagnostic laboratories

Amputation is commonly performed in an attempt to both treat and diagnose conditions affecting the digits of cats. The records of multiple veterinary diagnostic laboratories were searched to identify submissions of amputated digits from cats. Eighty-five separate submissions were reviewed for diagnosis, age, sex, limb of origin, and digits affected; and the original submitting clinics were surveyed to determine clinical outcome. The Kaplan-Meier product-limit method was used to determine the disease-free interval and survival time. Neoplastic disease was identified in 63 of 85 submissions, with exclusively inflammatory lesions composing the other 22 cases. In 60 (95.2%) of the neoplastic cases, a malignant tumor was identified. Squamous cell carcinoma was the most commonly identified malignant tumor (n = 15; 23.8%) and was associated with a median survival time of 73 days. Other diagnoses included fibrosarcoma (n = 14; 22.2%); adenocarcinoma, likely metastases of a primary pulmonary neoplasm (n = 13; 20.6%); osteosarcoma (n = 5; 7.9%); mast cell tumor (n = 4; 6.3%); hemangiosarcoma (n = 5; 7.9%); malignant fibrous histiocytoma (n = 2; 3.2%); giant cell tumor of bone (n = 2; 3.2%); and hemangioma (n = 2; 3.2%). Giant cell tumor of bone has not been previously described in the digits of cats. Various neoplasms can occur in the digits of cats, and submission of the amputated digit for histopathologic diagnosis is essential to determine the histogenesis and predict the clinical outcome.     

A matched observational study of canine survival with primary intraocular melanocytic neoplasia

A retrospective histopathologic study was performed to evaluate the effect of primary intraocular melanocytic neoplasia on canine survival. Tumor size, location within the globe, extent of infiltration, and mitotic index were analyzed for their potential to predict survival. A total of 244 cases of dogs with melanocytic tumors submitted to the Comparative Ocular Pathology Laboratory of Wisconsin from 1988 to 1998 were evaluated. Histopathologic criteria (mitotic index, cytologic features of anaplasia) were used to differentiate 188 benign melanocytomas from 56 malignant melanomas. Signalment evaluation of age, sex, and breed revealed similarities in both tumor populations, with the majority of tumors discovered in 9-year-old, female/spayed, mixed-breed dogs. A greater percentage of left eyes (66%) vs. right eyes (47%) was found in the melanoma population, but an equal distribution was found in the melanocytoma population (48% and 52%, respectively). The majority of tumors arose from the anterior uveal tract (79% in the melanocytoma and 95% in the malignant melanoma populations). The German Shepherd breed was predisposed in the limbal distribution. At the time of enucleation, most tumors had invaded the sclera, but did not show extrascleral extension (51% in the melanocytoma and 61% in the malignant melanoma populations). Survival analysis showed a significant difference in survival between control and malignant melanoma populations ( P  = 0.0081) and was suggestive of a difference between the melanocytoma and melanoma populations ( P  = 0.031). Tumor extension, tumor size, and mitotic index were not found to be reliable predictors of survival.     

Clinical study of cryosurgery efficacy in the treatment of skin and subcutaneous tumors in dogs and cats

Objective— To evaluate the efficacy of cryosurgery for treatment of skin and subcutaneous tumors in dogs and cats.
Study Design— Prospective study.
Animals— Dogs (n=20), cats (10).
Methods— Cutaneous or subcutaneous tumors were treated by liquid nitrogen cryosurgical spray (1 cm from target tissue at 90° until a 5-mm halo of frozen tissue was achieved) for 15–60 seconds. Malignant lesions had 3 freeze–thaw cycles benign tumors, 2 cycles. The second or third freeze cycle was performed after complete thaw of the preceding freeze. Wounds healed by second intention. Follow-up was weekly for 1 month and then twice monthly until wounds healed, and final outcome was determined by telephone interview of owners.
Results— Tumor size ranged from 0.3 to 11 cm diameter with 28 (60%) being 0.3–1 cm; 8 (17%) 1.1–3 cm, and 11 (23%) >3.4 cm. Complications included edema, erythema and for extremity lesions, pain and lameness. Treated lesions (n=47) had an overall remission of 98% (mean follow-up, 345±172.02 days [range, 150–750 days]). One malignant peripheral nerve sheath tumor recurred 7 months after cryosurgical treatment.
Conclusion— Cryosurgery is an efficient method for treatment of skin and subcutaneous tumors in dogs and cats.
Clinical Relevance— Cryosurgical ablation is an effective means of treating small cutaneous or subcutaneous tumors in dogs and cats, especially in older animals where wound closure or cosmetic outcome might limit surgical excision alone.     

Serum neopterin levels in female dogs with malignant mammary tumours

In this study, we have determined serum neopterin levels in female dogs with primary malignant mammary tumours. The study involved 50 female dogs which had a malignant mammary tumours removed surgically (32 animals with carcinoma, 12 animals with sarcoma and 6 animals with carcinosarcoma) and 10 clinically healthy female dogs. Serum neopterin levels were determined using a commercial ELISA kit. The mean neopterin levels were lower in the malignant tumour groups than in healthy animals but differences were statistically significant only in carcinoma and sarcoma groups. The decrease of neopterin levels in animals with malignant mammary tumours may suggest their decreased cellular immunity. Moreover, it might indicate that decreased activity of cellular mechanisms of the anti‐neoplastic response is one of the factors associated with the development and course of malignant mammary tumours in female dogs; however, further studies are necessary.     

Osseous lesions resembling vaccine-site sar comas in two cats

Extract

Lytic lesions with microscopic features similar to those of vaccine-site sarcomas were diagnosed in the distal femur of two young neutered male cats, one a 20-month-old Birman and the other an 18-month-old domestic short-hair (DSH). Radiographically, there was extensive destruction of trabecular and cortical bone in the metaphysis and/or epiphysis of the distal femur. The DSH cat also had angular deformity of the distal femur due to asymmetrical involvement of the physis. Histologically, the lesions in both cats consisted of dense, interwoven bundles of fibrous connective tissue, amongst which there were variable numbers of plump malignant mesenchymal cells, often with very large, hyperchromatic nuclei and irregularly shaped nucleoli. Several focal aggregates of small lymphocytes were present in both tumours. Although neither cat had apparently been vaccinated in the hindlimb it is possible that the tumours had been triggered by injection of some other irritant material.     

Treatment of spontaneous malignant tumours in dogs with PTMC

The chemical analysis of the caffeine salt of a phosphomolybdic-tungstic acid compound (PTMC) is described. Twenty-seven dogs with advanced malignant tumours have been treated with PTMC by intramuscular or intravenous injection. Five dogs - one case of metastatic osteosarcoma, two cases of metastatic mammary carcinoma, one case of metastatic squamous cell carcinoma and one case of primary fibrosarcoma showed objective tumour regression for periods varying from four weeks to 20 months. Only two of the 27 dogs treated showed toxic effects.     

Mortality in a cohort of flat-coated retrievers in the UK

A cohort study of 174 flat-coated retrievers was undertaken to establish the importance of cancer in flat coat mortality in terms of the prevalence of neoplasia in the breed and also the relative effect of cancer on lifespan in relation to other forms of mortality. Dogs aged 2–7 years were recruited in 1996 and followed until 2007. An annual health census was used to collect the data. Two dogs were lost to follow-up and 72 dogs (42%) died from confirmed neoplasia. Twenty dogs (11.6%) died of unconfirmed tumours and 61 (35%) died from non-neoplastic conditions. The cause of death was unknown for 19 dogs. Soft tissue sarcoma (especially histiocytic sarcoma) was the predominant cancer type, affecting 32 dogs (44% of neoplasms). Six dogs died with malignant melanoma and three with lymphoma. Median age at death was 9 years for dogs with tumours (eight for sarcoma patients) and 12 years for non-neoplastic fatalities. The results confirm that soft tissue sarcoma, particularly histiocytic sarcoma, is a major cause of mortality in this breed.     

Frequency of canine and feline tumors in a defined population.

The Tulsa Registry of Canine and Feline Neoplasms was the second animal tumor registry in the United States concerned with a defined population in a delimited geographic area. Only tumors histologically confirmed by registry pathologists were included in frequency statistics based on the annual dog and cat population presented to veterinarians. During the first registry year, about 1% of the 63,504 dogs and 0.5% of the 11,909 cats had one or more primary tumors. While the incidence rate for malignant tumors in dogs was similar to that in cats, the incidence of benign tumors of dogs was over 10 times that of cats. The most common tumors were sebaceous adenoma in dogs and lymphosarcoma in cats. Mammary cancer was the most common malignant tumor in dogs. Mammary tumors of female dogs were significantly more frequent in Pointers, Poodles and Boston Terriers, in that order, than in other breeds. A greater incidence of mammary tumors among intact compared to spayed female dogs was seen for virtually every age group except in the Pointer breed.     

Feline conjunctival melanoma: histopathological characteristics and clinical outcomes

Purpose  We report on the histopathology and clinical features of 21 cases of feline conjunctival melanoma.
Methods  A total of 18 cases are from the COPLOW collection and three cases from Antech Diagnostics. We tabulated the location of the tumor, pigmentation, cell shape, mitotic index and presence of multinucleated tumor cells. Surveys were sent to referring ophthalmologists to obtain further information about each case.
Results  The mean age of the cats was 12.4 years. A total of 11 cases were neutered males, six spayed females, and one each of intact female and male. Thirteen of the 21 cases were located on the bulbar conjunctiva, three on third eyelid only, three on palpebral conjunctiva. Sixteen tumors were pigmented while five were amelanotic. Seventeen of the cases consisted of round cell only while four cases were mixed populations of round and spindle cell. Fourteen of the cases contained multinucleated cells. The mitotic index ranged from 0 to 45 mitotic figures/10 HPF. Of the 13 cases with adequate follow-up information, four showed local recurrence while three reported metastasis. Eight cats had died at the time of the survey. Survival time post-diagnosis ranged from 0.5 to 36 months. Two cases had metastasized to the submandibular lymph nodes and in a third case, an abdominal mass was detected.
Conclusions  Feline conjunctival melanoma is most frequently found on the bulbar conjunctiva, are mostly round cells and suggest that conjunctival melanoma in cats has a poorer long term prognosis than the same neoplasm in dogs.     

Subtotal scapulectomy as the treatment for scapular tumour in the dog: a report of six cases

The medical records of six dogs treated by sub-total scapulectomy for tumours involving the scapula were reviewed. The mean age of dogs in this study was 8 years and 4 months. Clinical signs on presentation included lameness of the affected forelimb and a palpable mass over the scapular area on physical examination. Pre-operative chest and affected forelimb radiographs were taken in most cases in addition to a biopsy. Subtotal scapulectomy was performed, ensuring margins clear of neoplastic tissue of at least 2 cm, preservation of the glenoid cavity and thus retention of the scapulo-humeral joint. On histopathological examination the tumours where diagnosed as chondrosarcoma (one), haemangiosarcoma (two), anaplastic malignant neoplasia (one) and osteosarcoma (one). Limb function was found to be good in all cases postoperatively. Prognosis was related to histopathological diagnosis of the tumour, favourable with chondrosarcoma and poor with the other tumour types.     

Primary thoracic wall tumours of mesenchymal origin in dogs: a retrospective study of 46 cases

Forty-three of the chest wall tumours in 46 dogs were malignant; five had metastases apparent at the time of presentation, five more had metastases discovered intraoperatively. Surgical resection of the tumours was associated with a significantly better outcome than conservative management. The median survival times after surgery for dogs with osteosarcoma was 17 weeks, for dogs with fibrosarcoma it was 26 weeks and for dogs with chondrosarcoma it was 250 weeks. En bloc excision of primary tumours affecting the chest wall was associated with minimal morbidity, but long-term survival was limited by distant metastases, primarily to the lungs. The tumours recurred in only three dogs. Early, radical surgical excision is recommended in the management of tumours of the chest wall. The prognosis depends on the histologic type of tumour and a histological diagnosis is mandatory before excision.