Adjunctive bevacizumab therapy in an equine corneal stromal invasive squamous cell carcinoma with a 53-months follow-up.

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.

Characterization of the skin microbiome in normal and cutaneous squamous cell carcinoma affected cats and dogs.

Human cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) display microbial dysbiosis with an enrichment of staphylococcal species, which have been implicated in AK and SCC progression. SCCs are common in both felines and canines and are often diagnosed at late stages leading to high disease morbidity and mortality rates. Although recent studies support the involvement of the skin microbiome in AK and SCC progression in humans, there is no knowledge of this in companion animals. Here, we provide microbiome data for SCC in cats and dogs using culture-independent molecular profiling and show a significant decrease in microbial alpha diversity on SCC lesions compared to normal skin (P ≤ 0.05). Similar to human skin cancer, SCC samples had an elevated abundance of staphylococci relative to normal skin-50% (6/12) had >50% staphylococci, as did 16% (4/25) of perilesional samples. Analysis of Staphylococcus at the species level revealed an enrichment of the pathogenic species Staphylococcus felis in cat SCC samples, a higher prevalence of Staphylococcus pseudintermedius in dogs, and a higher abundance of Staphylococcus aureus compared to normal skin in both companion animals. Additionally, a comparison of previously published human SCC and perilesional samples against the present pet samples revealed that Staphylococcus was the most prevalent genera across human and companion animals for both sample types. Similarities between the microbial profile of human and cat/dog SCC lesions should facilitate future skin cancer research. IMPORTANCE: The progression of precancerous actinic keratosis lesions (AK) to cutaneous squamous cell carcinoma (SCC) is poorly understood in humans and companion animals, despite causing a significant burden of disease. Recent studies have revealed that the microbiota may play a significant role in disease progression. Staphylococcus aureus has been found in high abundance on AK and SCC lesions, where it secretes DNA-damaging toxins, which could potentiate tumorigenesis. Currently, a suitable animal model to investigate this relationship is lacking. Thus, we examined the microbiome of cutaneous SCC in pets, revealing similarities to humans, with increased staphylococci and reduced commensals on SCC lesions and peri-lesional skin compared to normal skin. Two genera that were in abundance in SCC samples have also been found in human oral SCC lesions. These findings suggest the potential suitability of pets as a model for studying microbiome-related skin cancer progression.

Intralesional interferon alpha-2b as a novel treatment for periocular squamous cell carcinoma in horses.

OBJECTIVE: To determine the safety and efficacy of perilesional human recombinant interferon alpha-2b (IFNα2b) for treatment of periocular squamous cell carcinoma (PSCC) in horses. ANIMALS STUDIED: Eleven horses (12 eyes) with PSCC were enrolled in this prospective clinical study with owner consent. PROCEDURES: Systemically healthy horses were included in the study following confirmation of PSCC via biopsy. Every two weeks for a maximum of six treatments, horses were sedated and perilesional injection of IFNα2b (10 million IU) was performed. Tumors were measured prior to each injection and at one, three, and 12 months after treatment completion. A greater than 50% reduction in tumor size was considered positive response to treatment (i.e., partial or complete response). Development of anti-IFNα2b antibodies was assessed using serum samples obtained after treatment initiation and compared with treatment responses. Antibody concentrations were analyzed using a mixed model. Statistical significance was considered p < 0.05. RESULTS: Each horse received four to six perilesional injections of IFNα2b. Five of 12 eyes (4/11 horses) responded to treatment. Two of five eyes showed complete resolution of gross PSCC. No systemic adverse effects were seen. Local swelling occurred during treatment protocol in 6/11 horses but resolved without intervention. All horses developed serum anti-IFNα2b antibodies. There was no evidence of statistical difference in antibody concentration between responders and non-responders. CONCLUSIONS: Perilesional administration of IFNα2b was found to be well-tolerated in horses with PSCC, and induced tumor regression in 42% of treated eyes. Treatment failure appears unrelated to the development of IFNα2b antibodies.

Expression of mPGES1 and p16 in feline and human oral squamous cell carcinoma: A comparative oncology approach.

Comparative cancer studies help us determine if discoveries in one species apply to another. Feline and human oral squamous cell carcinoma (FOSCC and HOSCC) are invasive tumours in which inflammation and abnormal p16 expression are reported. Immunohistochemistry was used to determine the expression of p16 and microsomal prostaglandin E2 synthase 1 (mPGES1) in 42 HOSCC and 45 FOSCC samples with known expression of cyclooxygenase 2 (COX2) and cluster of differentiation 147 (CD147). High p16 expression was more common in HOSCC tumour cells compared to adjacent stroma and oral epithelium (p < .05), with a similar but statistically nonsignificant pattern in FOSCC. Interestingly, high mPGES1 expression in FOSCC was more common in the adjacent epithelium compared to the other compartments (p < .05). In HOSCC, mPGES1 was more similar between compartments but was numerically more common in the tumour compartment (p > .05). There were nominal (p > 0.05) differences in marker expression between high and low mPGES1 expressing tumours in both species, including high p16 observed more commonly in high mPGES1 tumours, and COX-2 positive tumours being more common in low mPGES1 tumours. High CD147 HOSCC tumours were more common in the high mPGES1 HOSCC group (p < .05). In the FOSCC cohort, where there was no statistical difference in CD147 expression between high and low mPGES1 tumours, there were numerically higher CD147 cases in the high mPGES1group. Different expression patterns in FOSCC and HOSCC could be related to different risk factors. For example, p16 is a marker of papillomavirus-driven HOSCC, but a causal relationship between papillomaviruses and FOSCC has yet to be definitively demonstrated. The significance of high P16 expression in the absence of papillomavirus infection deserves further study, and the relative contributions of COX2 and mPGES1 to tumour inflammation and progression should be explored. The findings reveal potential similarities in FOSCC and HOSCC biology, while also demonstrating differences that may relate to risk factors and pathogenesis that are unique to each species.

Histologic, immunohistochemical, and in situ hybridization study of myxoid stroma in feline oral squamous cell carcinoma.

Oral squamous cell carcinoma (oSCC) is a highly invasive malignant neoplasm in cats. Recently, tumor stroma, known as tumor microenvironments, have been considered to play an essential role in tumor progression. However, their role in feline squamous cell carcinoma (SCC) remains unclear. This study aimed to reveal the cancer microenvironment of feline oSCC and evaluate the pathological mechanisms of progression. We used 19 samples from 17 cats with oSCC, which were examined using light microscopy, immunohistochemistry, and in situ hybridization (RNAscope®). Feline oSCCs had two types of stroma, namely fibrotic and myxoid stromal reaction patterns, which were easily distinguished using hematoxylin-eosin staining. The myxoid stroma was rich in hyaluronic acid, which seems to be produced by neoplastic cells. Furthermore, the presence of myxoid stroma was correlated with histological parameters, including the appearance of cancer-associated fibroblasts and tumor budding. Periostin protein expression was also frequently observed in the stroma of feline oSCC and was significantly more common in the myxoid stromal reaction pattern group than in the fibrotic group. Positive signals for periostin mRNA were detected in stromal cancer-associated fibroblasts. This study indicates that the interaction between neoplastic cells and stromal reaction pattern components, such as hyaluronic acid and periostin, may be involved in tumor malignancy. Therefore, we propose that focus be placed not only on the tumor tissue but also on the characterization of the stroma for analyzing feline oSCC.

Equus caballus papillomavirus type 2 (EcPV2)-associated benign penile lesions and squamous cell carcinomas.

BACKGROUND: Squamous cell carcinoma is the most common genital, ocular and gastric tumour in horses. Equus caballus papillomavirus type 2 (EcPV2) DNA has been detected in several studies in equine penile squamous cell carcinomas (SCCs) and precursor lesions providing evidence of a causal role of EcPV2 in equine genital SCCs. Recently, EcPV2 E6/E7 nucleic acids were also detected in equine gastric SCCs, but further studies are required to determine the role of EcPV2 infection in the pathogenesis of gastric SCC. EcPV2 nucleic acids have been rarely described in ocular SCCs and precursor lesions. OBJECTIVES: To investigate the presence of EcPV2 nucleic acids with polymerase chain reaction (PCR) and in situ hybridisation (ISH) in penile hyperplasias, papillomas and SCCs in horses and to determine whether EcPV2 nucleic acids can be detected in SCCs affecting other locations, including the stomach, ocular tissues and larynx. METHODS: Twenty-one archival formalin-fixed paraffin embedded (FFPE) tissue samples, including 12 genital lesions comprising penile hyperplasias, papillomas and SCCs, 6 ocular SCCs, 2 gastric SCCs and 1 laryngeal SCC, were screened by PCR and ISH for EcPV2 E6/E7 DNA and mRNA. Archival FFPE tissue samples (eyelid and penile mucosa and preputium) from six horses without a diagnosis or history of neoplastic or papillomavirus-associated disease were included as controls. RESULTS: EcPV2 nucleic acids were detected by PCR and ISH in all genital lesions (12/12) and gastric SCCs (2/2), in two ocular SCCs (2/6) and in one laryngeal SCC (1/1). In control horses, one eyelid sample was positive in PCR but not in ISH. The remaining control samples were negative for EcPV2 E6/E7 nucleic acids in PCR and ISH. CONCLUSIONS: These results further support the role of EcPV2 infection in the development of equine genital SCCs and suggest that EcPV2 infection may also act as a predisposing factor for other SCCs in horses, including gastric, ocular and laryngeal SCCs.

The effect of feeding a commercial feedstuff on gastric squamous gastric disease (ESGD) healing and prevention of recurrence.

Feedstuffs are often recommended to mitigate potential damage from acid associated with equine squamous gastric disease (ESGD). In acidic conditions, pectin alters its structure to one like mucus and binds the stomach mucosa, whilst alfalfa has a strong intrinsic acid buffering capacity. The study aimed to determine whether feeding a commercial beet pulp/alfalfa/oat fibre mix aids ESGD healing and/or prevention of recurrence. Ten adult horses with naturally occurring ESGD were included. All animals were treated with omeprazole as per the attending veterinarian's recommendation and randomly allocated to also be fed a commercial beet pulp/alfalfa/oat fibre mix (1Kg/horse divided into 2 meals/day; n=5) or no additional feed (n=5) for one month. Gastroscopy was then repeated to assess response to therapy. If the ESGD had healed, omeprazole therapy was discontinued, and the commercial feed given to all horses for a further month. Gastroscopy was repeated to determine ESGD recurrence. The mean (±SD) age of the horses was 11.6 (±3.8) years; 4 mares and 6 geldings; various breeds were represented; and the median (range) initial ESGD grade was 2 (2-4). ESGD had healed (grade 0/4) in all animals after one month. After a further month, ESGD had recurred in significantly (p=0.04) more animals that did not receive the commercial feed initially (3/5; 60%; mean [range] ESGD grade 3 [0,4]) compared to those that did (0/5; 0%; mean [range] ESGD grade 0 [0,0]). Thus, the commercial beet pulp/alfalfa/oat fibre mix aided prevention of ESGD recurrence when fed during the healing and prevention phases.

Claw bed inverted squamous papilloma associated with canine papillomavirus type 2 in a dog.

A claw bed inverted squamous papilloma (ISP) presented clinically as a swollen digit in a dog. Canine papillomavirus (CPV) type 2 was amplified by PCR and localised to the papilloma's epidermis using in situ hybridisation. This is the first report demonstrating a claw bed ISP caused by CPV.

Un papillome squameux inversé de la matrice unguéale est décrit cliniquement comme un gonflement du doigt chez un chien. Le papillomavirus canin (CPV) de type 2 a été amplifié par PCR et localisé dans l'épiderme du papillome par hybridation in situ. Il s'agit du premier rapport faisant état d'un papillome squameux inversé de la matrice unguéale par le CPV.

Um caso de papiloma escamoso invertido no leito ungueal em um cão apresentando aumento de volume em um dígito. O vírus do papiloma canino (CVP) Tipo 2 foi amplificado por PCR e localizado na epiderme do papiloma utilizando hibridização in situ. Este foi o primeiro relato demonstrando um papiloma escamoso invertido causado por CPV.

Un papiloma escamoso invertido del lecho ungueal se presentó clínicamente como un dedo hinchado en un perro. Se amplificó mediante PCR genoma del virus papiloma canino tipo 2 (CPV) y se localizó en la epidermis el papiloma mediante hibridación in situ. Este es el primer reporte de caso que demuestra la existencia de un papiloma escamoso invertido del lecho ungueal causado por CPV.

Gastroscopic characterisation and prevalence of gastric ulcer syndrome in working mules in Colombia.

BACKGROUND: The existing literature does not contain information about the prevalence of gastric ulcers in mules, and on the potential associations between the presence of ulcers and work load, work type, diet, sex, age and body condition score (BCS). OBJECTIVE: To estimate the prevalence and factors associated with mule gastric ulcer syndrome (MGUS) and evaluate its distribution in both mule squamous gastric disease (MSGD) and mule glandular gastric disease (MGGD) mucosa in a population of mules in Colombia. STUDY DESIGN: Observational, cross-sectional. METHODS: A total of 97 clinically healthy mules of different ages and locations in the province of Antioquia (Colombia) were included in this study. The mules were involved in agricultural activities (i.e., riding, pack and ranch mules) at the time of the study. The animals underwent gastroscopic evaluation, and ulcer scores from 0 to 4 were assigned based on severity, with scores ≥2 indicating clinical relevance. The presence or absence of ulcer in the squamous and/or glandular region of the stomach was recorded. Data related to work type, work load and diet, as well as sex, age and BCS were recorded for each mule. Pearson's chi-square test was used to determine the association between the outcomes and explanatory variables of the study (p ≤ 0.05). The results of the risk estimations were presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The frequency of MGUS in the study population was 42%. Most of the lesions were located in the squamous region of the stomach (27%), mainly in the margo plicatus, and 20% were located in the glandular region, mainly in the fundus and pyloric antrum. Six animals showed lesions in both squamous and glandular regions. Work load was the only variable associated with the presence of MGUS (OR: 1.98; 95% CI: 0.49-0.96) and MSGD (OR: 1.78; 95% CI: 0.36-0.67). Nevertheless, the findings did not provide any significant risk assessment result, nor did they reveal any significant interactions among the other variables. MAIN LIMITATIONS: This study used convenience sampling from a limited geographic region, and multivariate analysis was not performed, one of the exclusion criteria was the use of nonsteroidal anti-inflammatory drugs, which means that the effect of these drugs can no longer be evaluated. CONCLUSIONS: MGUS occurs in mules subjected to agricultural work, the risk factors associated with EGUS do not appear to be significant in mules and other equids subjected to the same conditions, in this region. Further research is needed to define the differential dynamics of MGUS in comparison with the findings in horses.

HISTORIAL: La literatura existente no contiene información sobre la prevalencia de úlceras gástricas en mulas, y sobre las potenciales asociaciones entre la presencia de ulceras y carga de trabajo, tipo de trabajo, dieta, sexo, edad y score de condición corporal (BCS). OBJETIVO: Estimar la prevalencia y factores asociados con síndrome de ulceración gástrica en mulas (MGUS) y evaluar su distribución tanto en la mucosa escamosa (MSGD) como glandular (MGGD) en una población de mulas en Colombia. DISEÑO DE ESTUDIO: Este estudio descriptivo observacional, seccional fue llevado a cabo por muestreo de conveniencia basado en estimación mínima de muestreo y una definición a priori con criterios de inclusión y exclusión. MÉTODOS: un total de 97 mulas clínicamente sanas de diferentes edades y localidades en la provincia de Antoquia (Colombia) fueron incluidas en este estudio. Las mulas estaban involucradas en actividades agrícolas (ie. monta, carga o rancho) en el momento de este estudio. Se les hizo una evaluación gastroscópica, se les dio un score de 0 a 4 basado en la severidad, con un score ≥2 indicando relevancia clínica. La presencia o ausencia de ulceras en la región escamosa y/o glandular del estomago fue anotada. Información relacionada con el tipo de trabajo, carga de trabajo y dieta, además del sexo, edad (joven, adulto, geriátrico), y el score de condición corporal fueron anotadas para cada mula. La prueba de Chi­cuadrado de Pearson fue usada para determinar la asociación entre los resultados y las variables explicativas del estudio (p ≤ 0.05). Los resultados de las estimaciones de riesgo fueron presentado como odds­ratios (ORs) con 95% de intervalo de confianza (CI). RESULTADOS: La frecuencia de MGUS en la población del estudio fue de 42%. Las mayoría de las lesiones fueron localizadas en la porción escamosa del estómago (27%), principalmente en el margo plicatus, y 20% fueron halladas en le región glandular, principalmente en el fondo y el antro pilórico. Seis animales presentaron lesiones en ambas regiones escamosa y glandular. La carga de trabajo estuvo variablemente asociada a la presencia de MGUS (OR: 1.98; 95% CI: 0.49­0.96) y MSGD (OR: 1.78; 95% CI: 0.36­0.67). Sin embargo, los hallazgos no proporcionaron resultados significativos de análisis de riesgo, y no revelaron ningunas interacciones entre las otras variables. LIMITACIONES PRINCIPALES: Este estudio utilizó muestreo de conveniencia de una región geográfica limitada, y no se llevaron a cabo análisis multivariados, un criterio de exclusión fue el uso de anti inflamatorios no esteroidales, lo que quiere decir que el efecto de estos fármacos ya no puede ser evaluado. CONCLUSIONES: MGUS ocurren en mulas haciendo trabajo agrícola, los factores de riesgo asociados a EGUS no parecen ser significativos en mulas y otros equinos sujetos a las mismas condiciones en esta región. Mas investigación es necesaria para definir la dinámica que diferencia a MGUS en comparación a los hallazgos en caballos.

Dilated pore of Winer in a dog.

A 9-year-old male neutered Goldendoodle was presented to the Animal Medical Center of Seattle with a history of a firm, hairless, cystic mass on the dorsal aspect of the neck. The mass had been present for 2 years and would periodically rupture and discharge moderate quantities of yellow-green, soft, semi-solid, keratinaceous material. As rupture of the mass was reported to cause the patient significant pain and discomfort, it was surgically excised. Histopathology of the mass revealed a bulbous keratin-filled cyst that communicated with the external environment via a small ostium. At the base of the cyst, the cyst lining was characterized by a markedly irregular and hyperplastic stratified squamous epithelium with an overt stratum granulosum and prominent, irregularly sized, shaped and spaced rete ridges. At the superficial aspect of the cyst near the ostium, the cystic lining was characterized by a relatively thinner stratified squamous epithelium with an overt stratum granulosum and regular basal contour. Based on the histomorphological appearance of the mass, a diagnosis of a dilated pore of Winer was made. Dilated pores of Winer are follicular cysts arising from the infundibulum of the hair follicle. They are relatively common in humans and uncommon in cats, and single case reports have been described in a horse and a woodchuck (Marmota monax). To the best of the authors' knowledge, this is the first description of a dilated pore of Winer in a dog.

Osteoinductive squamous cell carcinoma associated with a putative novel papillomavirus on the digit of a cat.

CASE HISTORY AND CLINICAL FINDINGS: An approximately 10-year-old, castrated male domestic short-haired cat developed swelling and ulceration of the second digit of the right front paw. Radiographs revealed a spherical soft tissue swelling with irregular distal margins that contained multiple lacy mineral opacities. The digit was amputated and submitted for histology. No recurrence has been observed 7 months after amputation. PATHOLOGICAL AND MOLECULAR FINDINGS: Histology revealed a moderately well-circumscribed proliferation of well-differentiated squamous cells arranged in trabeculae and nests. Numerous thin spicules of osseous metaplasia were visible throughout the neoplasm. Around 70% of the neoplastic cells contained papillomavirus-induced cell changes including large amphophilic cytoplasmic bodies and cells with shrunken nuclei surrounded by a clear halo. Intense p16CDKN2A protein immunostaining was visible within the neoplastic cells, suggesting papillomavirus-induced changes in cell regulation. A DNA sequence from a putative novel Taupapillomavirus type was amplified from the neoplasm. DIAGNOSIS: Osteoinductive squamous cell carcinoma associated with a putative novel papillomavirus type. CLINICAL RELEVANCE: The findings in this case increase the number of papillomavirus types known to infect cats, and the squamous cell carcinoma had histological features that have not been previously reported. The neoplasm was not as invasive as is typical for a squamous cell carcinoma and excision appeared curative. This is the first report of an osteoinductive squamous cell carcinoma of the skin of cats and the neoplasm had a unique radiographic appearance.

Monoclonal antibody cetuximab impairs matrix metalloproteinases 2 and 9, epithelial-mesenchymal transition and cell migration in feline oral squamous cell carcinoma in vitro.

Feline oral squamous cell carcinoma (FOSCC) is characterised by invasive and metastatic behaviour and is poorly responsive to current treatments, hence the need for new therapeutic strategies. FOSCC shares molecular targets with human head and neck squamous cell carcinoma (HNSCC), among these the epidermal growth factor receptor. Cetuximab is an anti-epidermal growth factor receptor monoclonal antibody employed in the therapy of HNSCC and, interestingly, previous work in vitro suggested that it displays cytostatic and cytotoxic properties also against FOSCC. With the present study, we aimed at further investigating the effects of cetuximab on invasion and metastasis pathways proven to be relevant in human patients. To this purpose, FOSCC cell lines SCCF1, SCCF2 and SCCF3 were treated with cetuximab for 48/72 h and subjected to Western blot for matrix metalloproteinases-2/9 (MMP-2/9) and epithelial-mesenchymal transition markers vimentin, E-, P- and N-cadherin. Treatment with cetuximab resulted in downregulation of MMP-2/-9 in all of the three cell lines in a dose-dependent manner. Moreover, cetuximab downregulated vimentin and P-cadherin in SCCF1, upregulated E-cadherin whilst downregulating P-/N-cadherins in SCCF2, and impaired P-/N-cadherins in SCCF3. An in vitro scratch test also demonstrated that cetuximab delayed cell migration in SCCF3. These data suggest that cetuximab mitigates invasion and metastasis processes by impairing MMPs and epithelial-mesenchymal transition pathways in FOSCC, indicating that this monoclonal antibody may help to counteract malignant progression and improve the management of locally invasive disease.

Different expression patterns of p63 and p73 in Felis catus papillomavirus type 2-associated feline Merkel cell carcinomas and other epidermal carcinomas.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor, and more than 90% of feline MCC cases test positive for Felis catus papillomavirus type 2 (FcaPV2). In the present study, basal cell markers p40, p63, and p73 and the stem cell marker SOX2 and cytokeratin 14 (CK14) were immunohistochemically examined in normal fetal, infant, and adult feline skin tissues. The expression of these proteins was examined in tumors positive for FcaPV2, including MCC, basal cell carcinoma (BCC), Bowenoid in situ carcinoma (BISC), and squamous cell carcinoma (SCC). Infant and adult feline skin tissues had mature Merkel cells, which were CK14-, CK18+, CK20+, SOX2+, synaptophysin+ and CD56+, while fetal skin tissue had no mature Merkel cells. MCC was immunopositive for p73, CK18, and SOX2 in 32/32 cases, and immunonegative for CK14 in 31/32 cases and for p40 and p63 in 32/32 cases. These results indicate that MCC exhibits different immunophenotypes from Merkel cells (p73-) and basal cells (p40+, p63+, and SOX2-). In contrast, all 3 BCCs, 1 BISC, and 2 SCCs were immunopositive for the basal cell markers p40, p63, and p73. The life cycle of papillomavirus is closely associated with the differentiation of infected basal cells, which requires the transcription factor p63. Changes in p63 expression in FcaPV2-positive MCC may be associated with unique cytokeratin expression patterns (CK14-, CK18+, and CK20+). Furthermore, SOX2 appears to be involved in Merkel cell differentiation in cats, similar to humans and mice.

Vulvar squamous cell carcinoma in a captive female chimpanzee: A case report.

A necropsy was performed on a 43-year-old female zoo chimpanzee, with cancer in the vulvar and perivulvar region. She was diagnosed with squamous cell carcinoma, the presence of this tumor in domestic animals and non-human primates is very rare in the vulvar region and there were no previous reports found on it in chimpanzee, due to which this report contributes to the knowledge on chimpanzee pathologies.

Cancer morbidity in Croatian cats: Retrospective study on spontaneously arising tumors (2009-2019).

One of the current leading causes of death in pet cats is neoplasia. The scarcity of data on tumor prevalence in cats from south-eastern Europe led to this retrospective study which reports an abundant collection of tumors diagnosed in cats living in Croatia. Archived histopathology findings (diagnosis, cell origin, and biological behavior), and epidemiological data (breed, sex, age, and anatomical site of the tumor) of the cats diagnosed with at least one tumor were collected and statistically analyzed. For the research, 2338 archived feline samples, obtained from 2009-2019, have been reviewed. In 659 samples (28.1%) one or more tumors were diagnosed. Tumors have most often affected non-pedigree cats, cats between 7 and 15 years of age, and female cats. Most tumors showed malignant behavior (85.7%). The most frequent diagnoses were mammary adenocarcinoma, lymphoma, and squamous cell carcinoma. Regarding origin, most samples were epithelial (46.9%), but mesenchymal (28.7%) and lymphoid tumors (17.0%) were also frequently found. Tumors most often occurred in the skin and subcutis, mammary gland (in females), digestive system, and hemolymphatic system (in males). Statistical analysis did not reveal breed, sex, and age predisposition, but female animals and non-pedigree cats were significantly more likely to develop malignant tumors. This detailed study gives insight into the most frequent tumors that occur in cats from Croatia, and the data reported here is likely applicable to other countries. This data will contribute to clinical veterinary oncology, as it presents the most extensive tumor index of cats in south-eastern Europe.

Gastrointestinal tract pathology of the owl monkey (Aotus spp.).

Owl monkeys are small nocturnal new world primates in the genus Aotus that are most used in biomedical research for malaria. Cardiomyopathy and nephropathy are well-described common diseases contributing to their morbidity and mortality; less is known about lesions affecting the gastrointestinal tract. Records from a 14-year period (2008-2022) at the Keeling Center for Comparative Medicine and Research were queried to identify instances of spontaneous gastrointestinal disease that directly contributed to the cause of death from the 235 adult owl monkeys submitted for necropsy. Of the 235, 10.6% (25/235) had gastrointestinal disease listed as a significant factor that contributed to morbidity and mortality. Diagnoses included candidiasis (3/25), gastric bloat (4/25), and intestinal incarceration and ischemia secondary (11/25), which included intussusception (4/25), mesenteric rent (3/25), strangulating lipoma (2/25), intestinal torsion (1/25), and an inguinal hernia (1/25). Intestinal adenocarcinomas affecting the jejunum (4/25) were the most common neoplasia diagnosis. Oral squamous cell carcinoma (1/25) and intestinal lymphoma (2/25) were also diagnosed. This report provides evidence of spontaneous lesions in the species that contribute to morbidity and mortality.

Metastasizing squamous cell carcinoma in a 50-year-old Eastern Hermann's tortoise (Testudo hermannii boettgeri).

A 50-year-old female Hermann's tortoise (Testudo hermannii boettgeri) was presented with anorexia and lethargy. Clinical examination revealed multiple, visually inconspicuous but indentable areas in the shell corresponding to osteolysis radiographically. Soft tissue nodules and osteolytic lesions were also noted in the limbs. Laboratory results revealed elevated aspartate aminotransferase activity and uric acid concentrations, hypoglycemia, and hyperphosphatemia. Klebsiella oxytoca was isolated from a biopsied scutal area, and the biopsy suggested neoplasia. After a short period of clinical improvement, the animal's condition deteriorated, and it died. Post mortem computed tomography revealed polyostotic lytic lesions of multiple bones and the shell with associated soft tissue nodules protruding into the coelom, and nodular lung lesions. Necropsy, histopathology, and immunohistochemistry secured a diagnosis of a poorly differentiated, pan-cytokeratin-positive squamous cell carcinoma with widespread soft tissue and bone metastases, osteolysis and desmoplasia.

Effect of a blend of magnesium oxide on Equine Squamous Gastric Disease in young trotter horses under training.

BACKGROUND: Equine squamous gastric disease (ESGD), as part of the equine gastric ulcer syndrome (EGUS), are common in racing horses. The use of buffering feed supplements to treat and/or prevent gastric ulcers is an option to control this condition. OBJECTIVE: The purpose of this study was to evaluate the effect of a 30-day supplementation with a blend of magnesium oxide (MgO) on ESGD scores in trotters under training. METHODS: Forty-two young trotters were submitted to a gastroscopic evaluation to assess their ESGD score and were randomly assigned in a group supplemented with MgO or in a control group. After 30 days, a second evaluation by gastroscopy was performed. The effect of the MgO supplementation was assessed by comparing the evolution of the ESGD score in supplemented and control groups between day 0 and day 30. RESULTS: The results confirm the high prevalence of EGUS in young Trotters. The supplementation significantly decreased the ESGD scoring in the supplemented group whereas the control group remain unchanged. CONCLUSION: The oral MgO supplementation was efficient to control ESGD in the population studied.

Altered E-cadherin/ß-catenin expression in feline cutaneous squamous cell carcinomas.

Cutaneous squamous cell carcinoma (CSCC) is the most common malignant skin tumour in cats and the nature of the molecular mechanisms involved is poorly defined. Included among the molecular mechanisms in human and canine CSCCs is altered expression of E-cadherin/ß-catenin. This study aimed to explore the immunohistochemical expression pattern of E-cadherin and ß-catenin in 43 samples of feline CSCC by using a tissue microarray to elucidate whether expression of these molecules is dysregulated. Membrane expression of E-cadherin and membrane and cytoplasmic expression of ß-catenin were significantly reduced in the CSCCs. Cytoplasmic expression of E-cadherin and nuclear expression of ß-catenin were also found in some CSCCs. These findings indicate that altered expression of E-cadherin and ß-catenin is a frequent event in feline CSCCs, suggesting that these molecules play an important role in acquisition of the malignant phenotype in feline patients with CSCC. The results also suggest the existence of a subpopulation of feline patients with CSCC in which the Wnt pathway may contribute to epidermal carcinogenesis.

[DDB2-associated incidence of squamous cell carcinoma in Haflingers: risk minimization by genotyping]. / DDB2-assoziiertes Vorkommen von Plattenepithelkarzinomen beim Haflinger: Risikominimierung durch Genotypisierung.

INTRODUCTION: SCC (squamous cell carinomas) are among the most common eye neoplasms in horses. In recent studies Haflinger horses with a homozygous genotype for a missense variant in the DDB2 gene (damage specific DNA binding protein 2) had a significant increased risk of developing ocular SCC. The aims of this study were to determine the frequency of the SCC-associated risk allele in the DDB2 gene in Swiss and Austrian Haflinger populations and to validate the previously described phenotypic correlation. For this purpose, Haflingers presented at various horse clinics in Switzerland (n = 21, including 11 SCC cases), privately kept Haflingers (n = 52, including 1 SCC case), and Haflingers from a stud farm in the Austrian Tyrol (n = 53) were recruited. The individual DDB2 genotype of the animals was determined using a polymerase chain ceaction (PCR) test using hair follicle or whole blood samples. Of the 12 horses suffering from SCC, nine had ocular SCC and three had non-ocular SCC. Six of the nine Haflingers with ocular SCC and one of the three Haflingers with non-ocular SCC were homozygous for the DDB2 variant. Of the 113 clinically normal animals, 7/113 were homozygous (6 %) and 42/113 were heterozygous (37 %), which corresponds to an allele frequency of 24,8 % in the control cohort. The risk of ocular SCC occurring in Haflingers is significantly increased with the homozygous DDB2 genotype. However, not all animals with SCC carry this gene variant and not all DDB2 homozygous animals develop SCC, which can be explained by the multifactorial genesis of the disease. Due to the high frequency of the undesirable allele, we recommend taking the individual DDB2 genotype of breeding animals into account in order to avoid homozygous offspring with a greatly increased SCC risk by excluding high-risk matings.

INTRODUCTION: Les carcinomes épidermoïdes (CE) sont parmi les néoplasmes oculaires les plus fréquents chez les chevaux. Des études récentes ont montré que les chevaux Haflinger présentant un génotype homozygote pour un variant faux-sens dans le gène DDB2 (damage specific DNA binding protein 2) avaient un risque significativement plus élevé de développer un CE oculaire. Les objectifs de cette étude étaient de déterminer la fréquence de l'allèle à risque associé au CE dans le gène DDB2 dans les populations suisses et autrichiennes de Haflinger et de valider la corrélation phénotypique décrite précédemment. Pour ce faire, des Haflingers présentés dans différentes cliniques équines en Suisse (n = 21, dont 11 cas de CE), des Haflingers privés (n = 52, dont 1 cas de CE) et des Haflingers d'un haras du Tyrol autrichien (n = 53) ont été recrutés. Le génotype DDB2 individuel des animaux a été déterminé à l'aide d'un test de réaction en chaîne par polymérase (PCR) utilisant des échantillons de follicules pileux ou de sang total. Sur les 12 chevaux souffrant de CE, neuf avaient un CE oculaire et trois un CE non oculaire. Six des neuf Haflingers atteints de CE oculaire et un des trois Haflingers atteints de CE non oculaire étaient homozygotes pour la variante DDB2. Sur les 113 animaux cliniquement normaux, 7/113 étaient homozygotes (6 %) et 42/113 étaient hétérozygotes (37 %), ce qui correspond à une fréquence d'allèle de 24,8 % dans la cohorte de contrôle. Le risque de CE oculaire chez les Haflingers augmente de manière significative avec le génotype DDB2 homozygote. Cependant, tous les animaux atteints de CE ne sont pas porteurs de cette variante génétique et tous les animaux homozygotes DDB2 ne développent pas de CE, ce qui peut s'expliquer par la genèse multifactorielle de la maladie. En raison de la fréquence élevée de l'allèle indésirable, nous recommandons de tenir compte du génotype DDB2 individuel des animaux reproducteurs afin d'éviter une progéniture homozygote présentant un risque fortement accru de CE en excluant les accouplements à haut risque.