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.

The prognostic significance of histologic and clinical features was evaluated in a retrospective study of 70 dogs treated with nephrectomy for renal cell carcinoma. Dogs presenting with hematuria and cachexia had significantly decreased overall and tumor-specific survival. Mitotic index (MI), nuclear size, nuclear pleomorphism, tumor differentiation, invasiveness, Fuhrman nuclear grade, and clear cell morphology were significantly associated with survival times (overall and tumor specific) in univariate analyses. A multivariate Cox proportional hazards model was constructed using stepwise selection to evaluate potential histologic predictor variables. This multivariate analysis revealed MI, defined as the number of mitotic figures in ten 400× fields, as the sole independent prognostic variable. Median survival for dogs with an MI >30 was 187 days compared with 1184 days for dogs with an MI of <10. Dogs with an intermediate MI of 10 to 30 had a median survival of 452 days. Canine renal carcinomas were categorized into the following subtypes based on histologic features and histochemical and immunohistochemical staining: (1) clear cell, (2) chromophobe, (3) papillary, and (4) multilocular cystic renal cell carcinomas. Clear cell carcinoma was diagnosed in 6 of 70 (9%) canine tumors and was associated with a significantly decreased median survival time. Papillary carcinomas were identified in 15 of 70 tumors (21%), chromophobe in 6 of 70 (9%), and the multilocular cystic variant of canine renal cell carcinoma in 3 of 70 tumors (4%). These findings facilitate uniform categorization of canine renal cell carcinoma and provide veterinary pathologists with criteria to determine prognostic information.

With the exception of solar-induced dermal hemangiosarcoma (HSA), the biologic behaviour of canine HSA is characterised by rapid tumour growth, a high metastatic rate and short survival times. Outcome of dogs with HSA of the tongue has not been previously reported. The purpose of this study was to assess outcome and prognostic factors in dogs with lingual HSA. Clinical data was collected retrospectively and histopathology was reviewed for 20 dogs. Median progression free survival was 524 days and the median overall survival time was 553 days. All dogs had low or intermediate grade tumours; most tumours were small and located on the ventral surface of the tongue. Prognostic factors significantly associated with increased survival included small tumour size and absence of clinical signs of an oral mass at the time of diagnosis. Dogs with HSA confined to the tongue may have a better prognosis compared with HSA in other organs.

This case series presents a unique and unreported variant of feline intestinal mast cell tumour recognized at the CSU Veterinary Diagnostic Laboratory. Fifty cases of feline intestinal mast cell tumours described as having a significant stromal component were reviewed. Neoplastic cells formed a trabecular pattern admixed with moderate to abundant dense stromal collagen (sclerosis). Neoplastic cells had poorly discernible intracytoplasmic granules which demonstrated metachromasia with special histochemical stains consistent with mast cell granules. Additionally, a subset of cases stained for mast cell-specific tryptase and c-kit demonstrated positive immunoreactivity. Eosinophilic infiltrates were moderate to marked in almost all cases. Lymph node and hepatic metastases were present in 66% of the cases. Treatment and clinical outcome was available in 25/50 cases. Twenty-three of these patients died or were euthanized within 2 months of initial diagnosis. This is the first case series to characterize a sclerosing variant of intestinal mast cell tumour in the cat which appears to have a high propensity for metastasis and a guarded prognosis.

Soft tissue sarcomas (STSs) develop from mesenchymal cells of soft tissues, and they commonly occur in the skin and subcutis of the dog. Although phenotypically diverse with frequently controversial histogenesis, STSs are considered as a group because they have similar features microscopically and clinically. Following resection, local recurrence rates are low in general but vary according to histologic grade and completeness of surgical margins. Complete margins predict nonrecurrence. Even most grade I STSs with “close” margins will not recur, but propensity for recurrence increases with grade. The frequency of metastasis has not been accurately estimated, but it is believed to be rare for grade I STSs and most likely to occur with grade III STSs. However, metastasis does not necessarily equate with poor survival. High mitotic index is prognostic for reduced survival time. Further research is needed to determine more precise estimates for recurrence rates and survival as related to completeness of surgical margins and to delineate potential differences in metastatic rate and median survival time between grades. Other potential indicators of prognosis that presently require further investigation include histologic type, tumor dimension, location, invasiveness, stage, markers of cellular proliferation, and cytogenetic profiles. Common issues limiting prognostic factor evaluation include biases from retrospective studies, small sample sizes, poor verification of metastasis, inconsistent STS classification and use of nomenclature, difficulties in differentiating STS phenotype, and diversity of the study population (stage of disease and treatment status).

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

Exocrine pancreatic carcinoma is a particularly malignant neoplasm of the dog. Clinical and pathologic findings of an unusual variant of exocrine pancreatic neoplasia termed hyalinizing pancreatic adenocarcinoma were evaluated in 6 dogs. On microscopic examination, neoplasms were composed of tubules and acini of epithelial cells, with bright eosinophilic granular apical cytoplasm. Tubular lumina and tumor stroma contained abundant hyaline material that resembled amyloid. The hyaline material was not congophilic, and tumor cells and hyaline material were immunohistochemically negative for amyloid A, immunoglobulin light chains (κ and λ), amylin (islet amyloid polypeptide), laminin, and α1-antitrypsin. Two patients survived longer than 15 months after diagnosis; one of these dogs was untreated and had grossly evident metastasis at the time of diagnosis. The deaths of the other 4 dogs occurred as a result of poor recovery after partial pancreatectomy or in association with other concurrent life-threatening conditions. Two dogs were diagnosed with panniculitis, a condition rarely associated with pancreatic disease. Further evaluation is needed to determine the composition and biologic significance of intratumor hyaline material. Studies that associate exocrine pancreatic carcinoma grade and histologic subtype with prognostic outcomes in the dog are warranted such that appropriate therapy can be elected.

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.

Staging of dogs with cutaneous mast cell tumours (MCTs) is an important diagnostic step. Aspiration of the liver and the spleen is often part of routine staging. This study cytologically compared mast cell numbers in fine-needle aspirates of liver and spleen of clinically normal unaffected dogs with those of dogs with cutaneous MCT and an ultrasonographically normal appearing liver and spleen. The unaffected dogs (n = 32) were selected from humane society dogs, and the affected dogs (n = 51) were selected from hospital cases. There were no statistically significant differences in each of the parameters evaluated for the liver aspirates. For splenic aspirates, affected dogs showed significantly more mast cells per cluster (P = 0.04) and more isolated mast cells per slide (P = 0.03) compared with unaffected dogs. However, no clinically important difference existed between the unaffected and affected dogs; thus, routine aspiration of an ultrasonographically normal appearing liver and spleen of dogs with cutaneous MCT does not appear to be a clinically useful staging tool.

OBJECTIVE:To evaluate extracorporeal intraoperative radiation therapy (IORT) as a treatment method for limb and joint sparing in dogs with appendicular sarcomas in sites other than the distal aspect of the radius.STUDY DESIGN:Retrospective study.ANIMALS:Thirteen client-owned dogs.METHODS:The bone tumor database and medical records (1998-2002) were reviewed for dogs with primary appendicular bone tumors treated with IORT limb-sparing surgery and adjuvant chemotherapy. The segment of bone containing the tumor was isolated from adjacent soft tissue and an osteotomy performed distant to the tumor. The bone segment was exteriorized, irradiated (70 Gy single fraction), and then stabilized with internal fixation. Adjuvant chemotherapy was administered. Lameness was graded and local and distant tumor control was determined. Associations between intra- and postoperative variables with complications and Kaplan-Meier survival analysis for median disease-free interval and survival time were calculated.RESULTS:Limb function was good or excellent in 10 dogs (77%). Postoperative complications (9 dogs, 69%) included deep infection, fracture of the irradiated bone, and implant failure. Surgical failure was more likely if a single implant was used to stabilize the osteotomized bone and if deep infection developed postoperatively. In 3 dogs, tumors recurred locally within bone in the radiation field. The disease-free and overall success rates of extracorporeal IORT for limb and joint preservation were 46% and 54%, respectively.CONCLUSIONS:Extracorporeal IORT provides a novel alternative to traditional techniques for preservation of joint and limb function in dogs with primary appendicular sarcomas. A minimum of 2 implants and intramedullary bone cement should be used to stabilize the osteotomized bone to minimize postoperative complications. Extracorporeal IORT should be used with caution in dogs with tumors of the distal tibia because of a high complication rate. Dogs with tumors in areas of good soft-tissue coverage, such as the humerus and femur, may be good candidates for limb and joint-sparing surgery using extracorporeal IORT.CLINICAL RELEVANCE:Extracorporeal IORT is a surgical technique that can be used for limb and joint salvage in dogs with primary appendicular sarcomas in sites usually not amenable to traditional limb-sparing techniques.

The purpose of this prospective clinical study was to quantify the surgical margin necessary to maximise local disease control for canine soft tissue sarcoma of various grades. This was achieved via gross and histopathologic studies. Fourteen dogs underwent surgical treatment for 15 localised, measurable, subcutaneous sarcomas. Surgery and histopathologic evaluation were performed to standardised protocols. Regular examinations for local recurrence and distant metastases were performed for at least 12 months postoperatively. One hundred percent local disease control was achieved with deep margins >10mm and 93% one year disease-free survival with wide margins (i.e. >10mm laterally and one fascial plane or >10mm in depth). There was one case of recurrence. Fascial planes appear to act as biological barriers to local tumour invasion but this protective effect may be overcome with high-grade lesions.

When external beam radiation therapy is administered to the pelvis, normal tissues irradiated may include the colon, small intestine, urethra, bladder, bone, and spinal cord. The objectives of this retrospective study were to determine the incidence and severity of late radiation effects following pelvic irradiation in dogs and to identify factors that increase the risk of these effects. Medical records of all dogs treated with curative intent external beam radiation therapy to the pelvic region between 1993 and 1999 were reviewed. Patients with follow-up longer than 9 months or any patient that developed late complications earlier than 9 months were evaluated. Sixteen dogs met criteria for inclusion in this study. All dogs were treated with a 6-MV linear accelerator with bilaterally opposed beams. Diseases treated included transitional cell carcinoma of the bladder, transitional cell carcinoma of the prostate, and anal sac apocrine gland adenocarcinoma. Four dose/fractionation schemes were used: 49.5 Gy in 3.3 Gy fractions, 54 Gy in 3.0 Gy fractions, 54 Gy in 2.7 Gy fractions, and 18 Gy intraoperative radiation therapy followed by 43 Gy external beam radiation therapy in 2.9 Gy fractions. Implantable chemotherapy in the form of an OPLA-Pt sponge was used in six dogs as a radiation potentiator. Colitis was the major late effect following pelvic irradiation, occurring in nine dogs (56%). Colitis was characterized as mild in three dogs, moderate in one dog, and severe in five dogs. Three of the dogs with severe effects suffered gastrointestinal perforation. All dogs with severe late effects received 3 or 3.3 Gy per fraction, and 80% received radiation potentiators. In the seven dogs that received 2.7 Gy or 2.9 Gy per fraction, late effects were classified as none (n = 5), mild colitis (n = 1), and moderate colitis (n = 1). Radiation therapy can be administered to the pelvic region with a minimal risk of late effects to the colon by giving smaller doses per fraction and avoiding systemic radiation potentiators.

This study was conducted to evaluate the toxicity and efficacy of Epidoxoform, a prodrug of the active metabolite of epidoxorubicin, in a mouse model of mammary carcinoma. A dose escalation trial established a maximal tolerated dose of 20 mg/kg given intraperitoneally (IP) to 6-8 week old female C3 HeJ mice. Two days following injection of 10(6) Gollin-B mouse mammary tumor cells into the mammary fat pad, Epidoxoform was given and tumor growth compared to mice treated similarly with. the maximum tolerated dose of epidoxorubicin and untreated controls. In all efficacy trials, a significant difference was found for tumor volume between Epidoxoform and epidoxorubicin treated mice and controls. In mice treated with a two-dose regimen, significantly increased efficacy was also found between Epidoxoform compared to epidoxorubicin. Epidoxoform appears to be efficacious in this model of mammary carcinoma, with improved efficacy over the parent compound epidoxorubicin. Further evaluation of this analogue appears warranted.

OBJECTIVE To determine outcome for dogs with grade-II mast cell tumors treated with surgery alone. DESIGN Retrospective study. ANIMALS 55 dogs. PROCEDURES Medical records were examined, and signalment; location and size of tumor; staging status; dates of local recurrence, metastasis, death, or last follow-up examination; status of surgical margins; previous surgery; postoperative complications; and cause of death were recorded. Follow-up information was obtained via reexamination or telephone conversations with owners or referring veterinarians. Univariate analysis was performed to identify prognostic factors. RESULTS 60 tumors in 55 dogs were included. Median follow-up time was 540 days. Three (5%) mast cell tumors recurred locally; median time to local recurrence was 62 days. Six (11%) dogs developed another mast cell tumor at a different cutaneous location; median time to a different location was 240 days. Three (5%) dogs developed metastases; median time to metastasis was 158 days. Fourteen dogs died; 3 deaths were related to mast cell tumor, and 7 were unrelated. The relationship with mast cell tumor was not known for 4. Median survival times were 151, 841, and 827 days, respectively, for these 3 groups. Forty-six (84%) dogs were free of mast cell tumors during the study period. A reliable prognostic factor could not be identified. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that additional local treatment may not be required after complete excision of grade-II mast cell tumors and that most dogs do not require systemic treatment.

The biocompatibility and levels of gentamicin released from a poly(lactic acid) (PLA) polymer system in the serum, milk and tissue of a food animal model were determined. Microsphere particles of PLA containing 6.7% (w/w) gentamicin were compressed into 5 mm beads onto suture. Three groups of three cull ewes each were implanted with a bead string of PLA/gentamicin in one caudal thigh (muscle) and PLA control beads in the opposite thigh for 2, 4 and 6 months. Milk and serum samples were obtained at regular intervals until sacrifice. Following sacrifice, implant sites, kidney, liver and skeletal muscle were sampled for gentamicin concentration and histologic evaluation. Serum gentamicin peaked by day 1 (up to 0.7 mug/mL) and decreased to near zero by day 16 in all groups. Milk levels were measurable (>0.01 mug/mL) only on 2 days, in one sheep. Kidney gentamicin levels approached 2 ppm, and liver gentamicin levels approached 1 ppm in the 6-month group. A mild to moderate foreign body reaction was seen histologically in all PLA/gentamicin and PLA control implantation sites. Gentamicin released from this implanted polymer system produced low serum and milk concentrations, but developed renal accumulation beyond tolerated levels (30 ppb). Polymer/antibiotic delivery systems show promise for the treatment of local infections in veterinary patients.