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Detecting loci under selection is an important task in evolutionary biology. In conservation genetics detecting selection is key to investigating adaptation to the spread of infectious disease. Loci under selection can be detected on a spatial scale, accounting for differences in demographic history among populations, or on a temporal scale, tracing changes in allele frequencies over time. Here we use these two approaches to investigate selective responses to the spread of an infectious cancer--devil facial tumor disease (DFTD)--that since 1996 has ravaged the Tasmanian devil (Sarcophilus harrisii). Using time-series 'restriction site associated DNA' (RAD) markers from populations pre- and post DFTD arrival, and DFTD free populations, we infer loci under selection due to DFTD and investigate signatures of selection that are incongruent among methods, populations, and times. The lack of congruence among populations influenced by DFTD with respect to inferred loci under selection, and the direction of that selection, fail to implicate a consistent selective role for DFTD. Instead genetic drift is more likely driving the observed allele frequency changes over time. Our study illustrates the importance of applying methods with different performance optima e.g. accounting for population structure and background selection, and assessing congruence of the results.

Repeatable head immobilization is important for minimizing positioning error during radiation therapy for veterinary patients with head neoplasms. The purpose of this retrospective cross-sectional study was to describe a novel technique for head immobilization (Device II) and compare this technique with a previously described technique (Device I). Device II provided additional support by incorporating three teeth (vs. two teeth with Device I). Between 2011 and 2013, both devices were applied in clinically affected cats (Device I, n = 17; Device II, n = 11) and dogs (Device I, n = 85; Device II, n = 22) of various breeds and sizes. The following data were recorded for each included patient: variability in the angle of the skull (roll, yaw, and pitch), coordinates of the isocenter, and distance from the reference mark to the tumor. Devices I and II differed for skull angle variability during the treatment of dogs (roll, P = 0.0007; yaw, P = 0.0018; pitch, P = 0.0384) and for yaw of during the treatment of cats (P < 0.0001). In each case, Device II was superior to Device I. The distance from the reference mark to the center of the tumor was significantly decreased for Device II vs. Device I (dogs, P < 0.0001; cats, P = 0.0002). Device II also provided more accurate coordinates for the isocenter. Authors recommend the use of, Device II for future clinical patients., (© 2015 American College of Veterinary Radiology.)

Background: Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival., Objectives: Evaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head., Animals: Twenty-one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head., Methods: Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2-8) were performed every other week until complete remission (CR) or tumor progression occurred., Results: Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively., Conclusions: Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco-regional strategies for cancer therapy in sensitive body regions such as periocular region., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Setup variability affects the appropriate delivery of radiation and informs the setup margin required to treat radiation patients. Twenty-four veterinary patients with head and neck cancers were enrolled in this prospective, cross-sectional study to determine the accuracy of an indexed board immobilization device for positioning. Couch position values were defined at the first treatment based on setup films. At subsequent treatments, patients were moved to the previously defined couch location, orthogonal films were acquired, table position was modified, and displacement was recorded. The mean systematic displacement, random displacement, overall displacement, and mean displacement values of the three-dimensional (3D) vector were calculated. Three hundred thirty-two pairs of orthogonal setup films were analyzed for displacement in cranial-caudal, lateral, and dorsal-ventral directions. The mean systematic displacements were 0.5, 0.8, and 0.5 mm, respectively. The mean random displacements were 1.0, 1.1, and 0.7 mm, respectively. The overall displacements were 1.1, 1.4, and 0.9 mm, respectively. The mean 3D vector value was 1.6 mm with a standard deviation of 1.2 mm. Ninety-five percent of the vectors were <3.6 mm. These values were compared to data obtained with a previously used immobilization device. A t-test was used to compare the two devices. The 3D vector, random displacement in all directions, and overall displacement in the cranial-caudal and dorsal-ventral directions were significantly smaller than displacements with the previous device. The precision and accuracy of the indexed board device was superior to the historical head and neck device., (© 2015 American College of Veterinary Radiology.)

Carotid body tumors (paragangliomas) arise from chemoreceptors located at the carotid bifurcation. In imaging studies, this neoplasm may be confused with other neck neoplasms such as thyroid carcinoma. The purpose of this retrospective, cross-sectional study was to describe computed tomographic (CT) and magnetic resonance imaging (MRI) characteristics of confirmed carotid body tumors in a multi-institutional sample of dogs. A total of 16 dogs met inclusion criteria (14 examined using CT and two with MRI). The most common reason for imaging was a palpable cervical mass or respiratory signs (i.e., dyspnea or increased respiratory noises). The most commonly affected breed was Boston terrier (n = 5). Dogs were predominantly male castrated (n = 10) and the median age was 9 years [range 3-14.5]. Most tumors appeared as a large mass centered at the carotid bifurcation, with poor margination in six dogs and discrete margins in ten dogs. Masses were iso- to hypoattenuating to adjacent muscles in CT images and hyperintense to muscles in T1- and T2-weighted MRI. For both CT and MRI, masses typically showed strong and heterogeneous contrast enhancement. There was invasion into the adjacent structures in 9/16 dogs. In six of these nine dogs, the basilar portion of the skull was affected. The external carotid artery was entrapped in seven dogs. There was invasion into the internal jugular vein in three dogs, and into the external jugular, maxillary, and linguo-facial veins in one dog. Imaging characteristics helped explain some clinical presentations such as breathing difficulties, Horner's syndrome, head tilt, or facial nerve paralysis., (© 2015 American College of Veterinary Radiology.)

Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

A 6-year-old female spayed Shetland Sheepdog presented for evaluation of a subcutaneous mass over the right prescapular region. The mass had been cytologically diagnosed as a lipoma by the referring veterinarian 20 months prior, but had grown significantly and was very firm. CT scan of the mass was suggestive of neoplasia; however, the tissue of origin could not be determined. Histopathologic evaluation diagnosed infiltrative angiolipoma, and marginal resection of the tumor was performed. Infiltrative angiolipomas are benign but locally aggressive neoplasms uncommonly reported in veterinary medicine. This report correlates the clinical, CT, and histopathologic characteristics of an infiltrative angiolipoma., (© 2014 American College of Veterinary Radiology.)

The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration., (© 2014 The Authors. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology Published by Wiley Periodicals, Inc.)

Histopathological and immunohistochemical examinations were made on a cutaneous tumor on the head of an 11-year-old female mixed-breed dog. The tumor was well demarcated and comprised multilobular structures of neoplastic epithelial cells with abundant plump peritumoral stromal cells. The neoplastic cells formed irregular cell cords or trabeculae and were arranged in characteristic palisades at the periphery. Immunohistochemically, neoplastic cells were positive for p63 and the several cytokeratins examined. In contrast, the plump peritumoral stromal cells were positive for vimentin and unevenly for nestin, a neuroepithelial stem cell protein. The stromal cells prominently proliferated in proximity to epithelial neoplastic cells, suggesting a close interaction between these two cell types.

Tumors involving the oral cavity of the horse are uncommon. No cases of equine adenocarcinoma on the dorsum of the tongue have been reported in the literature. We report a case of adenocarcinoma located on the dorsum of the posterior one-third of the tongue in a 29-year-old gelding with severe dysphagia. Endoscopy revealed an epiglottis involvement, and histology was consistent with adenocarcinoma arising from minor salivary glands, which was associated with a severe fungal colonization of affected tissues. The goals of this report are to present an uncommon case of dorsum of the tongue-associated neoplasia and to highlight the association with atypical fungal colonization, to review the literature and to discuss possible clinical approach and prognosis.

Tumours with skeletal-muscle differentiation are rare in companion animals. They are differentiated into benign rhabdomyomas and malignant rhabdomyosarcomas. A female German Holstein calf displayed a congenital, spherical, subcutaneous mass at the lateral side of the head. Histology revealed an encapsulated, expansile, highly cellular mass consisting of a reticular meshwork of moderately pleomorphic, small spindle-shaped to round cells within a fibrovascular to myxoid stroma as well as multifocal, large, blunt, multinucleated myotube-like cells (strap cells). Electron microscopy demonstrated characteristic cytoplasmic bundles of myofilaments and Z-stripes within the strap cells. Immunoreactivity for vimentin was observed in the small spindle-shaped cells and for desmin in the strap cells. The results are consistent with the spectrum of findings characteristic for a bovine congenital embryonal rhabdomyosarcoma.

Feline head and neck squamous cell carcinoma (SCC) is a loco-regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials., (© 2012 John Wiley & Sons Ltd.)

For canine and feline patients with head tumors, simultaneous irradiation of the primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often indicated. The purpose of this study was to assess the repeatability of a planning target volume (PTV) expansion protocol for these LNs. Two CT image sets from 44 dogs and 37 cats that underwent radiation therapy for head tumors were compared to determine LN repositioning accuracy and precision; planning-CT (for radiation therapy planning) and cone-beam CT (at the time of actual treatment sessions). Eleven percent of dogs and 65% of cats received treatment to their LNs. In dogs, the mandibular LNs were positioned more caudally (P = 0.0002) and the right mandibular and right retropharyngeal LNs were positioned more to the left side of the patient (P = 0.00015 and P = 0.003, respectively). In cats, left mandibular LN was positioned higher (toward roof) than the planning-CT (P = 0.028). In conclusion, when the patient immobilization devices and bony anatomy matching are used to align the primary head target and these LNs are treated simultaneously, an asymmetrical PTV expansion that ranges 4-9 mm (dogs) and 2-4 mm (cats), depending on the directions of couch movement, should be used to include the LNs within the PTV at least 95% of the time., (© 2012 Veterinary Radiology & Ultrasound.)

This case report describes the results of the gross pathological, histological and immunohistological examinations of a fibrosarcoma that spontaneously developed in the left neck region of an aged male Lewis rat that participated in a long-term facial nerve regeneration study. A 10 mm long polylactic acid (PLA) tube was implanted into a 7 mm critical defect gap of the buccal branch of the left facial nerve of a male eight-week-old Lewis rat. Forty-two weeks after implantation, an approximately 8 cm × 9 cm × 2.5 cm rapidly growing mass with ulceration of the overlying skin was found in the left neck region. Gross examination of the tumour and the surrounding tissues before tumour excision revealed that the tumour had clear boundaries, and had not invaded any facial tissues, the facial nerve and the PLA nerve guide. Gross examination of the tumour's cut surface revealed that the tumour comprised numerous smooth nodules with a homogeneous white tan colour. Examination of the haematoxylin and eosin-stained sections of the tumour revealed that the tumour was predominantly composed of bundles of spindle-shaped atypical proliferating cells that were mixed with bundles of collagen fibres and arranged in a storiform pattern. Tumour emboli and skin invasion were also observed. Immunohistological examination revealed that the tumour cells were weakly positive for vimentin, but negative for keratin, α-smooth muscle actin, S-100 protein and CD34. From the results of these analyses, the final pathological diagnosis of this tumour was a fibrosarcoma.

The purpose of this pilot study was to evaluate lymph node enhancement with an indirect magnetic resonance (MR) lymphography technique using 2 different contrast agents in the head and neck region of healthy dogs. Five dogs were imaged at various times after intradermal injection of gadoversetamide and Gadofluorine M (minimum of 1 week apart) in the right and left mandibular, temporal, and lateral neck regions. We observed consistent progressive enhancement with time in the mandibular, retropharyngeal, and superficial cervical lymph nodes. The node enhancement was comparable for both contrast agents. Contrast enhancement of the parotid lymph nodes was not seen. We conclude that this technique of indirect MR lymphography using either agent could be used to identify those lymph nodes at highest risk of metastatic disease in dogs with cancer, and to guide staging and treatment.

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity., (© 2011 Blackwell Publishing Ltd.)

A 5-year-old castrated male Labrador Retriever was presented to a referring veterinarian for a swelling in the neck region. Based on the results of histopathology, a carotid body tumor, was diagnosed. The dog was referred to a medical imaging unit for further staging and follow up. This report describes the magnetic resonance (MR) and computed tomographic (CT) appearance of a carotid body tumor.

In January 2010, 18 months after excision of an ocular squamous cell carcinoma (SCC), a Connemara mare presented with anorexia and periorbital/parotideal lesions. Post mortem examination revealed these lesions as forming one entity, with 2 additional growths in the retropharyngeal region and the left jugular groove, respectively. The lesions were confirmed histopathologically as SCCs. Using PCR, peripheral blood mononuclear cells (PBMCs) from 2008 and 2010, tumour tissue, intact skin and vulval mucosa were screened for Equus caballus papillomavirus type 2 (EcPV-2) and bovine papillomavirus types 1 and 2 (BPV-1/2) DNA. Whereas PBMCs from 2008 scored negative, EcPV-2 DNA was present in PBMCs and SCCs from 2010. Furthermore, reverse transcription PCR revealed EcPV-2 E6 transcripts in these samples. BPV-1/2 DNA, but not RNA, was demonstrated in the periorbital/parotideal mass, the SCC of the jugular groove, vulval mucosa and intact skin, but not in the pharyngeal SCC and PBMCs. Sequencing revealed a 99% similarity of EcPV-2 amplicons with the published EcPV-2 sequence. BPV-1/2 amplicons corresponded to BPV type 1. This report is the first to describe co-presence of BPV-1 and EcPV-2 DNA in a pony affected by an uncommon form of nongenital SCC, and the detection of EcPV-2 transcripts in lesions and PBMCs., (© 2011 EVJ Ltd.)

A 9-year-old, neutered male cat was presented for a subcutaneous mass on the neck. After surgical removal of the mass, a pet identification microchip was found within the tumour. Histological examination of the mass revealed typical features of the feline postinjection sarcoma. The cat had never received injections at the tumour site; all routine vaccinations were administered in the hindlimbs. Few cases of sarcomas developing at the site of microchip application have been reported in animals, although the contributory role of vaccine administrations has not been ruled out. This is the first report of a microchip-associated fibrosarcoma in a cat. Adherence to American Association of Feline Practitioners vaccination guidelines, avoiding the interscapular area, enabled confirmation of the definitive aetiology of the neoplasia., (© 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.)

Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumour regression in mouse models of squamous cell carcinoma (SCC). The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase (ODC) inhibitor, DFMO, and to determine whether this therapy results in reduction in tumour polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumour biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose (MTD) of MQT 1426 when combined with DFMO was determined. Dose-limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, two cats experienced objective tumour regression and six cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted., (© 2011 Blackwell Publishing Ltd.)

Ethical Issues: Caring for cancer patients presents many ethical issues for veterinarians and other veterinary health workers. The issues that most veterinarians think of relate to management of the patient when the owners' preferences for treatment do not appear to be in the animal's best interest, as well as concerns about toxicities and about costs of veterinary services (advanced imaging, surgery, radiation therapy and chemotherapy). While not limited to the veterinary profession, we are more often faced with dilemmas about the appropriateness of palliative care and decisions about euthanasia than our medical colleagues. Equally important are the ethics of not treating patients, and the integration of unproven and alternative strategies into conventional care. A separate ethical issue arises from investigational therapies and research. Less often considered, but nonetheless relevant, are the ethics of suboptimal evaluation (staging) of patients prior to treatment, or of not informing owners about all the options available., Client Communication: Ethical veterinary care is intertwined with good client communication. Without good communication, it is impossible, for example, to gain informed consent; and without informed consent, the ethics of cancer treatment are uncertain., Goal: This article, which draws in part on published research, where stated, and otherwise on the author's personal experiences/opinions and those of veterinary colleagues, is intended to provoke further thought and discussion on the ethics of caring for our cancer patients., (Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Three horses presented with variably painful, nonulcerated masses of the head or neck that were diagnosed as glomus tumours. Grossly, they were fleshy, pink to tan masses ranging from 0.4 to 9 cm in diameter, involving either the deep dermis and subcutis or the subcutis and underlying skeletal muscle. Microscopically, neoplastic epithelioid cells were arranged in sheets, cords and packets within lobules. The neoplastic cells frequently abutted and formed nodular bulges into large endothelium-lined vascular spaces, especially around the tumour periphery. Large nerve branches were associated with each tumour. As determined by immunohistochemistry, the neoplastic cells consistently expressed α-smooth muscle actin and vimentin, and some cells in two of the cases expressed desmin. A laminin- or collagen IV-positive basement membrane was demonstrated around individual tumour cells or small groups of cells in all three cases. Morphological features and immunohistochemistry supported the diagnosis of glomus tumour, most consistent with the solid type in humans. Applying a classification system used in humans, two of these tumours met criteria of malignancy (glomangiosarcomas). One horse was euthanized due to complications associated with recurrence and treatment-related necrosis and secondary infection., (© 2011 The Authors. Journal compilation © 2011 ESVD and ACVD.)

A common seagull (Larus fuscus) was found near the southern coast of Italy by the veterinarians of the local wild animal rescue center. Physical examination of the bird revealed an ulcerated mass involving a majority of the oral cavity; the mass did not allow for normal feeding. After the bird died necropsy was performed and the mass was histologically and immunohistochemically examined. The morphology and the immunoreactivity for Melan-A and S-100 antigens led to a diagnosis of malignant melanoma. This is the first case of malignant melanoma described in a seagull, and herein we compare the characteristics of the present case with malignant melanoma already described in domestic animals.

A six year-old intact female miniature poodle was presented with a soft mass of the forehead region. Computed tomography identified generalized frontal bone loss and a large extracranial mass, which had a low attenuation area of hemorrhagic necrosis with septation and enhancement of solid components. In magnetic resonance imaging, the mass was isointense in T1-weighted images except its fluid parts and hyperintense in T2-weighted images with lobulated by low-signal septa. Surgery was performed to remove the mass, and histopathologic examination revealed that the mass was consistent with undifferentiated pleomorphic sarcoma (malignant fibrous histiocytoma). The dog died from the rapidly recurrent mass and severe pulmonary metastasis.

Purpose: To investigate the effect of intratumoral administration of collagenase-2 on liposomal drug accumulation and diffusion in solid tumor xenografts., Methods: Correlation between tumor interstitial fluid pressure (IFP) and tumor physiological properties (size and vessel fraction by B-mode and Doppler ultrasound, respectively) was determined. IFP response to intravenous or intratumoral collagenase-2 (0.1%) treatment was compared with intratumoral deactivated collagenase-2. To evaluate drug accumulation and diffusion, technetium-99 m-((99m)Tc)-liposomal doxorubicin (Doxil) was intravenously injected after collagenase-2 (0.1 and 0.5%, respectively) treatment, and planar scintigraphic images acquired and percentage of the injected dose per gram tissue calculated. Subsequently, tumors were subjected to autoradiography and histopathology., Results: IFP in two-week-old head and neck squamous cell carcinoma xenografts was 18 ± 3.7 mmHg and not correlated to the tumor size but had reverse correlation with the vessel fraction (r = -0.91, P < 0.01). Intravenous and intratumoral collagenase-2 use reduced IFP by a maximum of 35-40%. Compared to the control, the low IFP level achieved through intratumoral route remained for a long period (24 vs. 2 h, P < 0.05). SPECT images and autoradiography showed significantly higher (99m)Tc-Doxil accumulation in tumors with intratumoral collagenase-2 treatment, confirmed by %ID/g in tumors (P < 0.05), and pathological findings showed extensive distribution of Doxil in tumors., Conclusions: Intratumoral injection of collagenase-2 could effectively reduce IFP in HNSCC xenografts for a longer period than using intravenous approach, which allowed for more efficient accumulation and homogeneous diffusion of the Doxil within the tumor interstitium.

A 9-year-old, female neutered Dalmatian was evaluated for acute onset of dyspnoea. Thoracocentesis on presentation yielded 1300 ml sanguineous fluid, while thoracic radiology and ultrasonography showed a mixed-echoic cavitary cranial mediastinal mass, sternal lymph node enlargement and pleural effusion. Surgical exploration of the thorax revealed a multi-lobulated red/brown cranial mediastinal mass and multiple similarly coloured ovoid nodules within several lung lobes. Histopathology revealed thymic branchial cysts with neoplastic transformation and examination of the lung was consistent with metastasis. Despite initially recovering well, acute sepsis and pyothorax resulted in cardiac arrest 8 days postoperatively. This is the first veterinary report of neoplastic transformation of a thymic branchial cyst with pulmonary metastasis., (© 2010 British Small Animal Veterinary Association.)

This case report describes the clinical, ultrasonographic and pathological findings in a five-year-old Swiss Braunvieh cow with extraskeletal chondroblastic osteosarcoma of the neck region. The cow was referred because of a firm, non-painful swelling, approximately 25 cm in diameter, which was situated mainly on the lower left side of the neck but extended to the right. Ultrasonographic examination of the mass revealed a chambered structure containing echoic material that was separated by hyperechoic septa. Chondroblastic osteosarcoma was diagnosed based on histological evaluation of a biopsy sample, and the diagnosis was confirmed by postmortem examination.

The potent anti-cancer agent doxorubicin (DOX) induces apoptosis of rapidly proliferating cells by inhibiting cellular proteasomes. The aim of the present study was to determine whether DOX modulates the level of expression and function of proteasomes in feline injection-site sarcoma (FISS). Tissue extracts from primary sarcoma lesions and the related healthy subcutis of 18 cats affected by FISS were investigated. Nine of these cats had received neoadjuvant DOX treatment and nine cats did not receive this therapy. There was enhanced proteasome expression in FISS, but this was not affected by administration of DOX. This finding may account for the low clinical effectiveness of DOX therapy in FISS and provides the rationale for developing new therapeutic protocols aimed at achieving better proteasomal inhibition in FISS and other tumours that respond poorly to DOX therapy., (Copyright 2010 Elsevier Ltd. All rights reserved.)

A case of neurofibroma is reported in a wild striped mullet Mugil cephalus. Macro- and microscopic features are described. The tumor arose on the head as a white-grayish, firm mass protruding outwards but covered by the epidermis. The neoplastic tissue showed well-defined borders and was encapsulated; it was predominantly composed of elongated cells with ellipsoid, hyperchromatic nuclei and pale cytoplasm. The cells were irregularly arranged; in the context of the neoplastic proliferation, these cells were usually densely packed, sometimes forming parallel arrays, but without distinctive nuclear palisades. The diagnosis of neurofibroma is also supported by the positive immunostaining for S-100 and vimentin as well as by the negative calretinin reaction.

A 4-month-old kitten was presented with a large mass over the temporal area involving the base of the left ear. Cytological evaluation of a fine-needle aspirate was not diagnostic. Computed tomography was used to determine tumor extent. Surgical resection was performed, which included parts of the orbital rim, masticatory muscles, the complete ear canal, and the pinna. Reconstruction of the ocular muscles was performed, and the skin defect was reconstructed using a single pedicle advancement flap. Despite unilateral facial paralysis, postoperative clinical function was excellent and aesthetics were good. Histological examination revealed the tumor to be a teratoma. After a follow-up period of 3 years, no signs of recurrence were evident. Extragonadal teratomas should be considered in the differential diagnosis when young animals are presented with a growing mass located outside the abdominal cavity. Surgical excision of a mature teratoma can be considered curative.

A 37-year-old yellow-crowned Amazon parrot (Amazona ochrocephala) and a 20-year-old red-lored Amazon parrot (Amazona autumnalis) each presented with a large mass localized on the lateral neck. With the first bird, there was no evidence of signs of pain or discomfort, and the bird prehended and swallowed food normally. The second bird showed signs of mild upper-gastrointestinal discomfort. Results of an ultrasound examination and aspiration of the mass on each bird revealed a cystic structure. A computed tomography performed on the second bird revealed a large polycystic mass connected to the pharynx by a lateral tract. During surgical resection, both masses were found to originate from the subpharyngeal area. Based on topography and the histopathologic and immunohistochemical results, the masses were determined to be a second branchial cleft cyst for the first case and a second branchial pouch cyst for the second case. In addition, a carcinoma was present in situ within the epithelium of case 1, and the cyst in case 2 was secondarily infected. Branchial cysts are uncommonly diagnosed in veterinary and human medicine. These 2 cases are the first documented in parrots and appear similar to second branchial cysts reported in adult humans.

Background: Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model., Methods: Canine cases entered in the Danish Veterinary Cancer Registry (DVCR) from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC). Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test., Results: A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown) were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128). Of these, 64 (50%) were malignant and 44 (34%) benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant), OMM (13; 20% of malignant), soft tissue sarcoma (11; 17% of malignant) and adenocarcinoma (5; 11% of malignant). The most common types of benign neoplasms were adenoma (7; 16% of benign), polyps (6; 14% of benign) and fibroma (5; 11% of benign)., Conclusions: In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans.Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and could be a clinical model for OMM in humans.

The positioning accuracy and precision of a head and neck immobilization device for radiation therapy of tumors in the canine skull was evaluated. Nineteen dogs with a spontaneous tumor of the head were enrolled including 12 with an intracranial mass and seven with an intranasal or maxillary tumor. Three hundred thirty-three pairs of orthogonal digital portal radiographs were analyzed to assess patient displacement in the cranial-caudal, lateral, and dorso-ventral directions. The mean systematic displacement was 0.8, 1, and 0.9 mm. The mean random displacement was 1.9, 1.6, and 1.5 mm. These values resulted in an overall displacement of 2.1 mm in the cranial-caudal direction, 1.8mm in the lateral direction, and 1.7 mm in the dorsal-ventral direction. The mean displacement value of the three dimensional (3D) vector was 2.4 mm with a standard deviation of 2.1. Ninety-five percent of all vectors were < 6.4 mm. This study quantifies the precision and accuracy of this particular positioning device. Knowing the limitations and setup variability of the system being used to set patients up for daily radiotherapy is paramount to planning and delivering appropriate radiation doses, especially as more complex treatment methods are used.

The current report describes a case of congenital subcutaneous and intramuscular tumors of the neck and tail base in a 4-week-old female Angus-Charolais crossbred calf. Results of clinical and ultrasound examination are summarized. Biopsy and necropsy findings indicated an infiltrative lipoma. Congenital lipomas are uncommon tumors in bovids. Clinical and morphologic differentials, as well as classification and the possible pathogenesis of congenital neoplasms, are discussed.

We examined the utility of a bite block-type head immobilization device, hereafter referred to as "head immobilization device", in order to improve the ease of immobilization and accuracy when performing radiotherapy for cranial tumors in animals. The head immobilization apparatus was a rectangular-shaped bite block-type device. We examined 55 cases in 46 dogs that underwent head CT scans between June 2005 and May 2006. The head immobilization device was used for 26 cases (immobilization group) and was not used for 29 cases (control group). Head stability was maintained in the control group by placing a towel under the head. We measured the angle of rotation of the xy, yz and xz planes for each group. The angles of rotation of the xy plane for the control and immobilization groups were 3.69 +/- 2.28 (mean +/- SD) and 1.39 +/- 1.50, respectively. The t-test demonstrated that the difference was statistically significant (p<0.001). These results indicate that there was reduced tilting to the left or right. We conclude that use of this head immobilization device was extremely easy and that it improved the accuracy of radiotherapy for cranial tumors in dogs and cats.

An eight-week-old male Sprague-Dawley (SD) rat showed signs of emaciation, and masses were found in the subcutis around the cervical and thoracic regions. At necropsy, a multilobular mass, 2.2 x 1.8 x 2.0 cm in size, had grown from the left neck into the thoracic cavity. On a cutting surface, masses were firm and whitish to tan, with necrotic and hemorrhagic plaques. Microscopically, masses were composed of multiple nodules of tumor cells that were incompletely encapsulated with fibrous connective tissue. The tumor cells exhibited varied forms, from spindle to globoid shapes with minimal to abundant eosinophilic cytoplasm, and appeared as large, multinucleated cells; many of the tumor cells were vacuolated. Histochemistry results revealed that tumor cells exhibited some cross-striation in the cytoplasm using PTAH staining. There were some multinuclear tumor cells with vacuoles located around the nuclei, and these vacuoles showed reddish staining by the periodic acid Schiff (PAS) method. Immunohistochemical staining also expressed intense granular cytoplasmic staining for desmin and myoglobin, with highly positive staining for PCNA, whereas alpha-smooth muscle actin (alpha-SMA) was negative. Based on the pathology results, a spontaneous rhabdomyosarcoma with pleomorphic type was diagnosed in a young SD rat.

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

Bleomycin and Interleukin 12 have been used clinically to treat tumors; however, the co-administration of Bleomycin and Interleukin 12 followed by electroporation has not been tested clinically. In this study, dogs with spontaneous head and neck tumors were treated with one co-administration of Bleomycin and Interleukin 12 plasmid DNA followed by electroporation. The regression of the recurrent papillary tumor and the adjacent metastatic bone tumor was analyzed by multiple CT scans. The papillary tumor was completely eradicated in less than 2 weeks, and the bone tumor was not visible 23 weeks after the administration.

A surgically excised biopsy representing a subcutaneous mass on the left side of the neck from a 3-year-old female European hedgehog (Erinsceus europaeus) was presented. Spontaneous myxosarcoma was diagnosed based on histological, immunohistochemical, and ultrastructural characteristics. The neoplasm grossly consisted of a firm, pale, multilobulated mass with a characteristic clear gelatinous fluid. Histologically, the neoplasm was nonencapsulated and composed of pleomorphic stellate or spindle-shaped vimentin and periodic acid-Schiff-positive cells arranged in loose sheets and occasionally whorls. The neoplastic cells were suspended in Alcian blue-positive stroma and contained infrequent mitotic figures. Evidence of a viral etiology was not detected using electron microscopy and polymerase chain reaction. This is the first case report of a myxosarcoma in a captive European hedgehog.

A 9-year-old, male French Bulldog was examined for a subcutaneous mass located at the site of a microchip implant. Cytologic examination of the mass was suggestive of a malignant mesenchymal neoplasm. Histologically, the mass was confirmed as a high-grade infiltrative fibrosarcoma, with multifocal necrosis and peripheral lymphoid aggregates. By immunohistochemistry, the sample was investigated for vimentin, smooth-muscle actin (SMA), CD3, CD79alpha, and CD18. All the neoplastic cells were positive for vimentin. Scattered cells at the periphery of the lesion were also positive for SMA, highlighting a myofibroblastic phenotype. The lymphoid cells were positive for CD18 and CD3. No aluminum deposits were detected by the aurintricarboxylic acid method. A diagnosis of fibrosarcoma morphologically similar to feline postinjection sarcomas was made. Fibrosarcomas at the site of injections have been reported in dogs and ferrets. Furthermore, neoplastic growth at the site of microchip implant in dog and laboratory rodents has been described.

Understanding the complex histological, genetic and molecular changes that lead to malignant transformation of squamous epithelia of the head and neck will likely guide the development of methods for improved diagnosis, monitoring and treatment of head and neck squamous cell carcinoma (HNSCC). The development and use of animal models that closely mimic the histopathology and molecular pathogenesis of HNSCC in humans would greatly expand the research possibilities and provide a means of testing potential therapeutic agents. However, many available animal models of HNSCC fall short of this objective. In order for investigators to select the appropriate model to answer scientific questions, it is important to understand the benefits and limitations of available animal models for the study of HNSCC. The purpose of this work is to give an overview of the most pertinent animal models of HNSCC, and to discuss future directions of research in this field., (2005 Wiley-Liss, Inc.)

Objectives: We sought to evaluate a minimally invasive contrast-assisted ultrasound (US) technique for sentinel lymph node (SLN) localization., Methods: Microbubble contrast medium was injected into peritumoral tissues in 10 dogs with spontaneous head or neck tumors. Regional lymph nodes (LNs) were imaged up to 20 minutes after contrast administration using power Doppler US. Comparative lymphoscintigraphy studies were performed in all dogs by peritumoral injection of 99mTc-sulfur colloid administered around the primary lesion., Results: US contrast enhancement of SLN revealed sentinel nodes and associated lymphatics in 8 of 10 dogs. In each instance in which contrast-enhanced LN was identified with US, a corresponding SLN was detected by lymphoscintigraphy. Multiple SLNs were present in 2 dogs. Regional lymph nodes were positive for metastasis in 1 dog and reactive in 9 dogs., Conclusions: Contrast-assisted US is effective in localizing SLN. This technique could reduce or eliminate many of the limitations of current SLN detection procedures.

Four cases of neoplasms in the heads of old dogs were studied. All the dogs showed both carcinomatous and sarcomatous malignant components in an admixed growing pattern. Histologic analysis of the tumors showed that the carcinomatous cells resembled squamous cell carcinoma in all dogs except one, where an adenoid arrangement of the neoplastic cells was also observed. The sarcomatous component showed osteoid matrix produced by pleomorphic poorly differentiated cells, which is regarded as a typical feature of osteosarcomas. Immunohistochemical analysis demonstrated that the components were positive only for cytokeratin (carcinomatous component) or vimentin (sarcomatous component). This observation led us to classify the neoplasms as true carcinosarcomas, thus providing evidence of a new preferential location for this unusual tumor in dog.

Paclitaxel is used as a single agent, and in combination with other drugs, as a standard of care in the treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the use of paclitaxel for therapy of SCCHN may be accompanied by serious side effects. Paclitaxel is a known cytotoxic inhibitor of cell proliferation that acts by stabilizing microtubules and inducing apoptosis. Opioid growth factor (OGF), [Met(5)]-enkephalin, is an endogenous peptide that has tonically active inhibitory effects on the growth of SCCHN in vitro and in vivo. OGF action is rapid, reversible, mediated by the nuclear-associated OGF receptor (OGFr), and is not cytotoxic (nor apoptotic related). The present study was designed to examine whether a combination of chemotherapy with paclitaxel and biotherapy with OGF is more effective than either agent alone in inhibiting tumor growth. Moreover, focus was placed on whether there are changes in the side effects known to occur with paclitaxel alone, following this combined therapy. Human SCC-1 cells, derived from a well differentiated SCCHN, were transplanted into athymic mice. The mice were randomized to receive intraperitoneal (i.p.) injections of sterile saline (controls), OGF (10 mg/kg, daily), paclitaxel (8 mg/kg, every other day), or both paclitaxel (8 mg/kg, every other day) and OGF (10 mg/kg, daily) beginning on the day of tumor inoculation. OGF, but not paclitaxel, delayed measurable and visible tumor appearance of mice with SCCHN. Treatment with paclitaxel, but not with other agents, had a marked effect on the body weights. Survival only was reduced in the paclitaxel group, with an average life span of 34.3+/-3.1 days recorded, in comparison to the 50-day survival (date of termination) for all other groups. Beginning after week 4 of tumor inoculation and drug treatment, the tumor weight of the paclitaxel/OGF group was significantly reduced from the control, OGF, and paclitaxel-exposed mice. The OGFr number of the SCCHN tumors was 2.1-fold greater in the animals exposed to OGF or paclitaxel, and elevated 38% in the paclitaxel/OGF group; significant differences from the control group were found for the OGF and paclitaxel groups. These data suggest that combined chemotherapy (i.e., paclitaxel) and biotherapy (OGF) provides a valuable alternative to the standard of care for SCCHN patients.