Single high-dose radiation therapy and liquid fiducial markers can be used in dogs with incompletely resected soft tissue sarcomas.

OBJECTIVE: To evaluate the outcome and effects of single high-dose radiation therapy with the aid of liquid fiducial markers in dogs following resection of soft tissue sarcomas (STSs). ANIMALS: 36 client-owned dogs. METHODS: Dogs with a histologic diagnosis of a grade II or III STS that underwent liquid fiducial guided single fraction, 20-Gy stereotactic radiation therapy following surgical excision of an STS between May 2017 and March 2019 were prospectively enrolled in this study. Data collected from the medical records included patient signalment, tumor-related information, treatment details, and outcome. Kaplan-Meier survival analysis was performed for overall survival time (OST) and disease-free interval (DFI). The median OST and DFI were not reached, so restricted mean OST and DFI were also calculated. RESULTS: 36 dogs were included in the study. All dogs underwent radiation therapy a mean of 36.1 days (range, 20 to 59 days) after surgery. Acute and delayed radiation toxicity effects occurred in 80.5% and 36.1% of dogs, respectively, all of which affected the skin. Tumor recurrence was noted in 24.3% of dogs with a median time to recurrence of 272 days (range, 14 to 843 days). The restricted mean OST was 1,556 days (range, 1,383 to 1,728 days) and restricted mean DFI was 1,330 days (range, 1,101 to 1,559 days). CLINICAL RELEVANCE: The results of this study showed that administering a single 20-Gy fraction of radiation in combination with a liquid fiducial marker to treat marginally or incompletely resected STS in the absence of gross disease resulted in similar OST and DFI compared to other previously reported radiation protocols.

Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody.

BACKGROUND: Osteosarcoma (OS) represents the most common primary bone tumor in humans and in companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend the survival of patients with OS. Here, we examine the dosimetry in beagle dogs and cross-reactivity with human tissues of a novel human antibody, IF3, that targets the insulin growth factor receptor type 2 (IGF2R), which is overexpressed on OS cells, making it a candidate for radioimmunotherapy of OS. METHODS: [89Zr]Zr-DFO-IF3 was injected into three healthy beagle dogs. PET/CT was conducted at 4, 24, 48, and 72 h. RAPID analysis was used to determine the dosimetry of [177Lu]Lu-CHXA"-IF3 for a clinical trial in companion dogs with OS. IF3 antibody was biotinylated, and a multitude of human tissues were assessed with immunohistochemistry. RESULTS: PET/CT revealed that only the liver, bone marrow, and adrenal glands had high uptake. Clearance was initially through renal and hepatobiliary excretion in the first 72 h followed by primarily physical decay. RAPID analysis showed bone marrow to be the dose-limiting organ with a therapeutic range for 177Lu calculated to be 0.487-0.583 GBq. Immunohistochemistry demonstrated the absence of IGF2R expression on the surface of healthy human cells, thus suggesting that radioimmunotherapy with [177Lu]Lu-CHXA"-IF3 will be well tolerated. CONCLUSIONS: Image-based dosimetry has defined a safe therapeutic range for canine clinical trials, while immunohistochemistry has suggested that the antibody will not cross-react with healthy human tissues.

Characterization of IGF2R Molecular Expression in Canine Osteosarcoma as Part of a Novel Comparative Oncology Approach.

Progress in prognostic factors, treatments, and outcome for both canine and human osteosarcoma (OS) has been minimal over the last three decades. Surface overexpression of the cation independent mannose-6-phosphate/insulin-like growth factor receptor type 2 (IGF2R) has been proven to occur in human OS cells. Subsequently, radioimmunotherapy (RIT) targeting IGF2R has demonstrated promising preliminary results. The main aims of this study were to investigate the expression of IGF2R in spontaneously occurring canine OS cells using immunohistochemistry (IHC) on archived biopsy samples and to assess its prognostic significance. Thirty-four dogs were included in the study. All cases showed that 80-100% of OS cells stained positive for IGF2R. IGF2R overexpression alone was not shown to have prognostic significance using both visual and quantitative methods of IHC staining intensity. This study has established for the first time the consistent expression of IGF2R in spontaneously occurring canine OS. This comparative oncology approach will allow further investigation into RIT as a novel treatment modality; first in canines and then in humans with OS. In addition, further studies should be performed to assess the true prognostic significance of IGF2R overexpression.

Identification of potential plasma protein biomarkers for feline pancreatic carcinoma by liquid chromatography tandem mass spectrometry.

In both humans and cats, pancreatic carcinoma is an aggressive cancer with a grave prognosis. Proteomics techniques have successfully identified several blood-based biomarkers of human pancreatic neoplasia. Thus, this study aims to investigate whether similar biomarkers can be identified in the plasma of cats with FePAC by using liquid chromatography tandem mass spectrometry (LC-MS/MS). To facilitate evaluation of the low abundance plasma proteome, a human-based immunodepletion device (MARS-2) was first validated for use with feline plasma. Marked reduction and/or complete removal of albumin and immunoglobulins was confirmed by analysis of electrophoretograms and mass spectral data. Subsequently, plasma collected from 9 cats with pancreatic carcinoma (FePAC), 10 cats with symptomatic pancreatitis, and 10 healthy control cats was immunodepleted and subjected to LC-MS/MS. Thirty-seven plasma proteins were found to be differentially expressed (p < .05 in one-way ANOVA, FC >2 in fold change analysis). Among these proteins, ETS variant transcription factor 4 (p < .05) was overexpressed, while gelsolin (p < .01), tryptophan 2,3-dioxygenase (p < .05), serpin family F member 1 (p < .01), apolipoprotein A-IV (p < .01) and phosphatidylinositol-glycan-specific phospholipase D (p < .05) were down-regulated in cats with FePAC. Further studies on these potential biomarkers are needed to investigate their diagnostic value.

Novel Human Antibodies to Insulin Growth Factor 2 Receptor (IGF2R) for Radioimmunoimaging and Therapy of Canine and Human Osteosarcoma.

Etiological and genetic drivers of osteosarcoma (OS) are not well studied and vary from one tumor to another; making it challenging to pursue conventional targeted therapy. Recent studies have shown that cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed in almost all of standard and patient-derived OS cell lines, making it an ideal therapeutic target for development of antibody-based drugs. Monoclonal antibodies, targeting IGF2R, can be conjugated with alpha- or beta-emitter radionuclides to deliver cytocidal doses of radiation to target IGF2R expression in OS. This approach known as radioimmunotherapy (RIT) can therefore be developed as a novel treatment for OS. In addition, OS is one of the common cancers in companion dogs and very closely resembles human OS in clinical presentation and molecular aberrations. In this study, we have developed human antibodies that cross-react with similar affinities to IGF2R proteins of human, canine and murine origin. We used naïve and synthetic antibody Fab-format phage display libraries to develop antibodies to a conserved region on IGF2R. The generated antibodies were radiolabeled and characterized in vitro and in vivo using human and canine OS patient-derived tumors in SCID mouse models. We demonstrate specific binding to IGF2R and tumor uptake in these models, as well as binding to tumor tissue of canine OS patients, making these antibodies suitable for further development of RIT for OS.

Assessment of neutrophil function in canine cancer patients undergoing chemotherapy and correlation with neutrophil numbers.

Decreased neutrophil function following administration of chemotherapy has been reported in dogs with lymphoma. The first objective of our study was to determine if neutrophil oxidative burst and phagocytic activity are affected by chemotherapy 7 to 10 days following initiation of treatment in dogs with lymphoma and non-lymphoma malignancies. The second objective was to determine if there is a correlation between neutrophil numbers and neutrophil function before or after initiation of chemotherapy. Flow cytometric assessment of neutrophil oxidative burst and phagocytosis following stimulation with Escherichia coli was performed in 9 dogs diagnosed with lymphoma and 17 non-lymphoma tumor-bearing dogs pre- and post-chemotherapy, as well as 14 tumor-free control dogs. Spearman rank correlation was performed to determine if blood neutrophil numbers and neutrophil function were significantly correlated. Lymphoma patients showed significantly reduced percentage neutrophil oxidative burst post-chemotherapy compared to healthy controls as well as compared to pre-chemotherapy values (P = 0.0022 and P = 0.0020, respectively). Lymphoma patients also exhibited significantly reduced neutrophil phagocytosis activity post-chemotherapy compared to controls and pre-chemotherapy values (P = 0.0016 and P = 0.014, respectively). Dogs with non-lymphoma malignancies also showed a significant decrease in both percentage oxidative burst and phagocytosis post-chemotherapy compared to pre-chemotherapy values (P = 0.00040 and P = 0.029, respectively). Neutrophil numbers and function were not significantly correlated. The results of the study suggest that chemotherapeutic treatment decreases neutrophil oxidative burst and phagocytic activity 7 to 10 days post-treatment in dogs with various malignancies. Furthermore, neutrophil numbers cannot be used to predict neutrophil function.

Une diminution de la fonction des neutrophiles après l'administration d'une chimiothérapie a été rapportée chez des chiens atteints de lymphome. Le premier objectif de notre étude était de déterminer si la stimulation oxydative des neutrophiles et l'activité phagocytaire sont affectées par la chimiothérapie 7 à 10 jours après le début du traitement chez les chiens atteints de lymphomes et de tumeurs malignes non lymphomateuses. Le deuxième objectif était de déterminer s'il existe une corrélation entre les nombres de neutrophiles et la fonction des neutrophiles avant ou après le début de la chimiothérapie. L'évaluation par cytométrie en flux de la stimulation oxydative des neutrophiles et de la phagocytose après stimulation par Escherichia coli a été réalisée chez neuf chiens diagnostiqués avec un lymphome et 17 chiens avec des tumeurs non lymphomateuses avant et après la chimiothérapie, ainsi que 14 chiens témoins sans tumeur. Une corrélation des rangs de Spearman a été effectuée pour déterminer si les nombres de neutrophiles sanguins et la fonction des neutrophiles étaient significativement corrélés. Les patients atteints de lymphome ont montré un pourcentage significativement réduit de stimulation oxydative des neutrophiles après la chimiothérapie par rapport aux témoins sains ainsi que par rapport aux valeurs pré-chimiothérapie (P = 0,0022 et P = 0,0020, respectivement). Les patients atteints de lymphome ont également présenté une activité de phagocytose par les neutrophiles significativement réduite après la chimiothérapie par rapport aux témoins et aux valeurs pré-chimiothérapie (P = 0,0016 et P = 0,014, respectivement). Les chiens atteints de tumeurs malignes non lymphomateuses ont également montré une diminution significative du pourcentage de stimulation oxydative et de la phagocytose post-chimiothérapie par rapport aux valeurs pré-chimiothérapie (P = 0,00040 et P = 0,029, respectivement). Les nombres et la fonction des neutrophiles n'étaient pas significativement corrélés. Les résultats de l'étude suggèrent que le traitement chimiothérapeutique diminue la poussée oxydative des neutrophiles et l'activité phagocytaire 7 à 10 jours après le traitement chez les chiens atteints de diverses tumeurs malignes. De plus, les nombres de neutrophiles ne peuvent pas être utilisés pour prédire la fonction des neutrophiles.(Traduit par Docteur Serge Messier).

Radioimmunotherapy Targeting IGF2R on Canine-Patient-Derived Osteosarcoma Tumors in Mice and Radiation Dosimetry in Canine and Pediatric Models.

BACKGROUND: Osteosarcoma (OS) has an overall patient survival rate of ~70% with no significant improvements in the last two decades, and novel effective treatments are needed. OS in companion dogs is phenotypically close to human OS, which makes a comparative oncology approach to developing new treatments for OS very attractive. We have recently created a novel human antibody, IF3 to IGF2R, which binds to this receptor on both human and canine OS tumors. Here, we evaluated the efficacy and safety of radioimmunotherapy with 177Lu-labeled IF3 of mice bearing canine-patient-derived tumors and performed canine and human dosimetry calculations. METHODS: Biodistribution and microSPECT/CT imaging with 111In-IF3 was performed in mice bearing canine OS Gracie tumors, and canine and human dosimetry calculations were performed based on these results. RIT of Gracie-tumor-bearing mice was completed with 177Lu-IF3. RESULTS: Biodistribution and imaging showed a high uptake of 111In-IF3 in the tumor and spleen. Dosimetry identified the tumor, spleen and pancreas as the organs with the highest uptake. RIT was very effective in abrogating tumor growth in mice with some spleen-associated toxicity. CONCLUSIONS: These results demonstrate that RIT with 177Lu-IF3 targeting IGF2R on experimental canine OS tumors effectively decreases tumor growth. However, because of the limitations of murine models, careful evaluation of the possible toxicity of this treatment should be performed via nuclear imaging and image-based dosimetry in healthy dogs before clinical trials in companion dogs with OS can be attempted.

Equine small intestinal angiomatosis.

Multiple red, raised nodules multifocally distributed along the serosal surface of the normal and the nonviable jejunum were identified in a 24-year-old neutered male horse undergoing surgery for removal of the strangulating lipoma around the jejunum. Histologically, these nodules consisted of many significantly and variably dilated, blood-filled vascular channels lined by a single layer of flattened, well-differentiated endothelial cells with occasional thrombi within a mildly thickened fibrous stroma. A diagnosis of intestinal angiomatosis was proposed. To the best of the authors' knowledge, this is the second report of small intestinal angiomatosis in a horse.

Angiomatose du petit intestin équin. De multiples nodules rouges surélevés distribués de manière multifocale le long de la surface séreuse du jéjunum viable et non-viable furent identifiés chez un cheval mâle castré âgé de 24 ans soumis à une chirurgie pour le retrait d'un lipome étranglant autour du jéjunum. Histologiquement, ces nodules consistaient en de nombreux canaux vasculaires remplis de sang dilatés de manière significative et variable, et tapissés par une couche unique de cellules endothéliales aplaties et bien différenciées avec à l'occasion des thrombi à l'intérieur d'un stroma fibreux légèrement épaissi. Un diagnostic d'angiomatose intestinale fut proposé. Au meilleur de la connaissance des auteurs, ceci constitue le deuxième rapport d'angiomatose du petit intestin chez un cheval.(Traduit par Dr Serge Messier).

Extraskeletal osteosarcoma associated with a benign hair follicle tumor in a dog.

A rare presentation of an extraskeletal osteosarcoma, suspected to have evolved from chronic inflammation associated with a benign hair follicle tumor in a dog is described. The patient was treated with surgical excision, carboplatin, and toceranib. The patient had an extended disease-free interval and a survival time of 45.4 months.

Ostéosarcome extra-squelettique associé avec une tumeur bénigne d'un follicule pileux chez un chien. On décrit la rare présentation d'un ostéosarcome extra-squelettique, suspecté d'avoir évolué à partir d'une inflammation chronique associée à une tumeur bénigne d'un follicule pileux chez un chien. Le patient fut traité avec excision chirurgicale, carboplatine et toceranib. Le patient eut un intervalle prolongé exempt de maladie et un temps de survie de 45,4 mois.(Traduit par Dr Serge Messier).

Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors.

Osteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines. We aimed to assess efficacy and safety of treating PDX and commercial OS tumors in mice with radiolabeled antibody to IGF2R and to investigate IGF2R expression on canine OS tumors. IGF2R expression on human commercial lines 143B and SaOS2 and PDX lines OS-17, OS-33 and OS-31 was evaluated by FACS. The biodistribution and microSPECT/CT imaging with 111Indium-2G11 mAb was performed in 143B and OS-17 tumor-bearing SCID mice and followed by radioimmunotherapy (RIT) with 177Lutetium-2G11 and safety evaluation. IGF2R expression in randomly selected canine OS tumors was measured by immunohistochemistry. All OS cell lines expressed IGF2R. Biodistribution and microSPECT/CT revealed selective uptake of 2G11 mAb in 143B and OS-17 xenografts. RIT significantly slowed down the growth of OS-17 and 143B tumors without local and systemic toxicity. Canine OS tumors expressed IGF2R. This study demonstrates the feasibility of targeting IGF2R on OS in PDX and spontaneous canine tumors and sets the stage for further development of RIT of OS using comparative oncology.

Peritoneal fluid immunocytochemistry used for the diagnosis of a possible case of equine gastrointestinal B-cell lymphoma.

After physical examination, ultrasonographic evaluation of thorax and abdomen, and peritoneal fluid analysis, gastrointestinal neoplasia with suspected diffuse peritoneal metastasis was diagnosed in a 17-year-old Arabian gelding. The owner elected euthanasia and declined postmortem examination. Immunocytochemistry analysis of the peritoneal fluid resulted in a diagnosis of B-cell lymphoma.

Immunocytochimie du liquide péritonéal utilisée pour le diagnostic d'un cas possible de lymphome gastro-intestinal à cellules B. Après un examen physique, une évaluation échographique du thorax et de l'abdomen et une analyse du liquide péritonéal, une néoplasie gastro-intestinale avec métastase péritonéale diffuse suspectée a été diagnostiquée chez un hongre arabe âgé de 17 ans. Le propriétaire a choisi l'euthanasie et a refusé l'examen postmortem. L'analyse par immunohistochimie du liquide péritonéal a donné lieu à un diagnostic de lymphome à cellules B.(Traduit par Isabelle Vallières).

A comparative proteomic study of plasma in feline pancreatitis and pancreatic carcinoma using 2-dimensional gel electrophoresis to identify diagnostic biomarkers: A pilot study.

While pancreatitis is now recognized as a common ailment in cats, the diagnosis remains challenging due to discordant results and suboptimal sensitivity of ultrasound and specific feline pancreatic lipase (Spec fPL) assay. Pancreatitis also shares similar clinical features with pancreatic carcinoma, a rare but aggressive disease with a grave prognosis. The objective of this pilot study was to compare the plasma proteomes of normal healthy cats (n = 6), cats with pancreatitis (n = 6), and cats with pancreatic carcinoma (n = 6) in order to identify potential new biomarkers of feline pancreatic disease. After plasma protein separation by 2-dimensional gel electrophoresis, protein spots were detected by Coomassie Brilliant Blue G-250 staining and identified by mass spectrometry. Alpha-1-acid glycoprotein (AGP), apolipoprotein-A1 (Apo-A1), and apolipoprotein-A1 precursor (Pre Apo-A1) appeared to be differentially expressed, which suggests the presence of a systemic acute-phase response and alteration of lipid metabolism in cats with pancreatic disease. Future studies involving greater case numbers are needed in order to assess the utility of these proteins as potential biomarkers. More sensitive proteomic techniques may also be helpful in detecting significant but low-abundance proteins.

Bien que la pancréatite soit maintenant reconnue comme un problème peu fréquent chez les chats, le diagnostic demeure un défi étant donné les résultats discordants et la sensibilité sous-optimale de l'échographie et de l'épreuve spécifique de la lipase pancréatique féline (Spec fPL). La pancréatite partage également des similarités cliniques avec le carcinome pancréatique, une maladie rare mais agressive ayant un pronostic grave. L'objectif de cette étude pilote était de comparer les protéomes plasmatiques de chats normaux en santé (n = 6), de chats avec une pancréatite (n = 6), et de chats avec un carcinome pancréatique (n = 6) afin d'identifier de nouveaux biomarqueurs potentiels de maladie pancréatique féline. Après séparation des protéines plasmatiques par électrophorèse en gel en deux dimensions, les taches de protéines furent détectées par coloration avec du bleu brillant de Coomassie G-250 et identifiées par spectrométrie de masse. La glycoprotéine acide alpha-1 (AGP), l'apolipoprotéine A1 (Apo-A1), et le précurseur de l'apolipoprotéine A1 (Pre Apo-A1) apparaissent comme étant exprimées de manière différentielle, ce qui suggère la présence d'une réponse de phase-aiguë systémique et une altération du métabolisme des lipides chez les chats avec une maladie pancréatique. Des études additionnelles regroupant un plus grand nombre de cas sont nécessaires afin d'évaluer l'utilité de ces protéines comme biomarqueurs potentiels. Des techniques plus sensibles de protéomique pourraient également être utiles pour détecter des protéines significatives mais de faible abondance.(Traduit par Docteur Serge Messier).

Hemorrhagic cystitis in a dog receiving carboplatin.

An 8 yr old castrated male Labrador retriever mixed-breed dog with osteosarcoma (OSA) of the left proximal humerus receiving carboplatin presented 10 days after the third chemotherapy treatment with hematuria, stranguria, and pollakiuria. A presumptive diagnosis of hemorrhagic cystitis was made based on clinical signs, urinalysis, and cytologic analysis of a traumatic catheterization sample. Carboplatin was removed from the chemotherapy treatment plan and was substituted with doxorubicin. The dog was treated with meloxicam for pain, and the cystitis signs subsided over a period of 4 wk. Carboplatin is commonly used as adjuvant chemotherapy for dogs with OSA following amputation and is not known to cause hematuria in dogs, although there are reports of this occurring in humans. To the authors' knowledge, there are no reports in the veterinary literature of this toxicity.

Intraocular sarcoma associated with a rupture lens in a rabbit (Oryctolagus cuniculus).

This case report describes the clinical manifestations and ocular pathology of an intraocular sarcoma in a spayed female 7-year-old rabbit that developed clinical signs consistent with phacoclastic uveitis at 6 months of age, which was left untreated for most of the next 6 years. Ophthalmologic examination confirmed pupillary occlusion, aqueous flare, fibrin, and lens debris within the anterior chamber of the right eye. The right eye was blind and phthisical. The tentative clinical diagnosis was chronic phacoclastic uveitis, and a routine transconjunctival enucleation of the right eye was completed. The globe was formalin-fixed and submitted for histologic examination. Light microscopic examination revealed a ruptured cataractous lens, uveitis, retinal detachment, and an intraocular sarcoma centered around the lens. Immunohistochemical (IHC) staining was positive for smooth muscle actin and vimentin and negative for Desmin and cytokeratin intermediate filaments.

Effects of a standardized anesthetic protocol on hematologic variables in healthy cats.

This study evaluated the effects of an anesthetic protocol using intravenous ketamine and midazolam, and intramuscular buprenorphine on hematologic variables in cats. Twelve healthy adult cats had blood collected for a complete blood count before and after the induction of anesthesia. There were significant decreases in red blood cell counts, hemoglobin concentrations and hematocrits after the induction of anesthesia. On average, red blood cell counts and hematocrits decreased by 25%, and hemoglobin concentrations decreased by 24%. Based on hematocrit, 3/12 samples (25%) taken while the cats were anesthetized would have been interpreted as belonging to anemic patients while none of the cats would have been considered anemic before anesthesia. This study suggests that a complete blood count performed on blood taken under anesthesia with this anesthetic protocol should be interpreted cautiously in order to not make a false diagnosis of anemia.

Respiratory distress due to retropharyngeal and neck swelling in a horse with mediastinal lymphosarcoma.

A 9-year-old, 1494-lb (679-kg) Quarter horse gelding in good body condition was admitted to the Veterinary Teaching Hospital, Western College of Veterinary Medicine (WCVM), University of Saskatchewan, for evaluation and treatment of acute respiratory distress. On a trail ride 26 days before presentation, the gelding had been exposed to a horse with clinical signs of an upper respiratory tract infection. The gelding performed well on the trail ride but, 4 days later, developed a mild swelling in the retropharyngeal area and a slight bilateral mucoid nasal discharge. The gelding was examined at the farm by its primary veterinarian, who made a presumptive diagnosis of strangles. Treatment was initiated using a combination of trimethoprim/sulfamethoxazole (30 mg/kg PO q12h for 1 week) and phenylbutazone (6 mg/kg PO q24h for the first 2 days, followed by 3.5 mg/kg PO q24h for 5 more days). The gelding did not respond satisfactorily to antimicrobial and antiinflammatory therapy. During the following 2 weeks, the retropharyngeal swelling gradually became more pronounced and extended to the upper portion of the neck. Two days before presentation at WCVM, the gelding also developed a dry cough with difficult breathing, and the retropharyngeal and neck swelling extended to the pectoral region and ventral pectoral area extending to the cranial ventral abdomen. Because of progressing clinical signs and poor response to treatment, the horse was referred to WCVM for further evaluation.

What is your diagnosis? Intracranial mass in a dog.

A 9-year-old, spayed female Chihuahua was presented for evaluation of acute, progressive neurologic disease. On physical examination the dog was depressed and laterally recumbent. The dog had marked neutrophilia with a toxic left shift and monocytosis. Using computed tomography with contrast enhancement a large intracranial mass lesion was identified in the rostral portion of the brain. The mass extended from the central thalamic region rostral to the cribiform plate and obliterated the lateral ventricles. A fine needle aspirate of the mass contained moderately pleomorphic polygonal cells with many intranuclear cytoplasmic pseudoinclusions (ICPs). The primary differential diagnosis was meningioma, based on cell morphology and the presence of ICPs. At necropsy, the mass was well-demarcated, unencapsulated, and densely cellular. Cells were arranged in papillary projections on fibrovascular stalks, and eosinophilic ICPs and nuclear folding were frequently seen. Cavitated areas of necrosis throughout the tumor mass were filled with intact and degenerated neutrophils. The histopathologic diagnosis was malignant papillary meningioma. ICPs are not frequently observed in Wright-stained cytologic preparations but may be found in many types of neoplasms, including meningiomas.

A dog with squamous cell carcinoma in the middle ear.

An 8-year-old, castrated male golden retriever was referred for lethargy and inappetance. Severe pain was elicited on palpation of the left temporomandibular joint region. Computed tomography revealed aggressive bone destruction of the left bulla. Squamous cell carcinoma was diagnosed. Malignant tumor in the canine middle ear is rare.