Effects of morphine on histamine release from two cell lines of canine mast cell tumor and on plasma histamine concentrations in dogs with cutaneous mast cell tumor

OBJECTIVE To determine the effects of morphine on histamine release from 2 canine mast cell tumor (MCT) cell lines and on plasma histamine concentrations in dogs with cutaneous MCTs. ANIMALS 10 dogs with cutaneous MCT and 10 dogs with soft tissue sarcoma (STS). PROCEDURES The study consisted of 2 phases. First, 2 canine MCT cell lines were exposed to 3 pharmacologically relevant morphine concentrations, and histamine concentrations were determined by an ELISA. Second, dogs with MCT or STS received 0.5 mg of morphine/kg, IM, before surgery for tumor excision. Clinical signs, respiratory rate, heart rate, arterial blood pressure, rectal temperature, and plasma histamine concentrations were recorded before and 5, 15, 30, and 60 minutes after morphine administration but prior to surgery. Data were compared by use of a 2-way ANOVA with the Sidak multiple comparisons test. RESULTS In the first phase, canine MCT cell lines did not release histamine when exposed to pharmacologically relevant morphine concentrations. In the second phase, no differences were noted for heart rate, arterial blood pressure, and rectal temperature between MCT and STS groups. Plasma histamine concentrations did not significantly differ over time within groups and between groups. CONCLUSIONS AND CLINICAL RELEVANCE No significant changes in histamine concentrations were noted for both in vitro and in vivo study phases, and no hemodynamic changes were noted for the in vivo study phase. These preliminary results suggested that morphine may be used safely in some dogs with MCT.

Prevalence and distribution of canine neoplastic and non-neoplastic cutaneous lesions in Serbia: a retrospective study of 2432 Cases (2011 – Mid 2021)

Cutaneous lesions, especially skin tumors in dogs, are among the most common lesions in this animal species. The aim of this study was to identify the most common types of canine cutaneous lesions, to determine the absolute and relative frequency of each type of cutaneous lesion, anatomical locations, mean age, as well as gender and breed distribution. The examination included all samples of cutaneous lesions in dogs obtained by surgical biopsy in veterinary clinics and examined at the Laboratory of the Department of Pathology at the Faculty of Veterinary Medicine, University of Belgrade from the 1st January 2011 to the 1st July 2021. In this period (126 months), a total of 2432 samples of cutaneous lesions were examined, of which 1984 (81.58%) were tumors (1037/1984, 52.27% benign and 947/1984, 47.73% malignant) and 448 (18.42%) non-neoplastic cutaneous lesions. The most commonly found cutaneous tumors were: mast cell tumor (17.34% of all tumors), histiocytoma (9.78%), papilloma (7.91%), lipoma (7.81%), squamous cell carcinoma (7.36%), trichoblastoma (4.44%), hepatoid adenoma (4.39%) and malignant melanoma (4.18%). The most common non-neoplastic cutaneous lesions were: follicular cyst(s) (35.04% of all non-neoplastic lesions), pyogranulomatous chronic dermatitis (23.88%), lymphocytic dermatitis (7.37%), hyperkeratosis (4.24%), and granulomatous dermatitis (3.79%). Our results substantially confirm previously reported data regarding cutaneous neoplastic and nonneoplastic lesions in dogs, and provide updated information on their frequency, animal age, anatomic location and breed distributions.

Immunohistochemical and molecular profiling of CD 117, Oct-4, and Sox-2 in canine cutaneous mast cell tumor of the crossbred dogs in Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand

Background and Aim: CD 117 (c-KIT) internal tandem duplication (ITD), octamer-binding transcription factor 4 (Oct-4), and sex-determining region Y-box 2 (Sox-2) may govern the oncogenicity and aggressiveness of canine cutaneous mast cell tumor (MCT) in the crossbred dogs. Thus, a comprehension of this matter may help us establishing a novel platform to treat the disease in those dogs. However, evidence has lacked so far. Thus, this study aimed to survey CD 117 ITD, Oct-4, and Sox-2 expressions and their relations to the 2-tier grading in a group of Thai crossbreed dogs. The study was done using polymerase chain reaction (PCR), Reverse transcription PCR (RT-PCR), and immunohistochemistry. Materials and Methods: Thirty-three MCT specimens graded by the 2-tier histopathology grading were collected from the crossbred and purebred dogs. CD 117 ITD was detected by conventional PCR and immunohistochemistry. While, Oct-4 and Sox-2 expression levels were determined at the protein and mRNA levels by immunohistochemistry and RT-PCR, respectively. The expression magnitude of each parameter was then related to the grades and breeds. Results: About 60.61% of specimens were low grade, while 39.39% were high grade. CD 117 ITD was not detected in all specimens. A significant increase of Oct-4 expression was found in the high-grade, crossbred dogs. Meanwhile, Sox-2 expressions were increased both in the purebred and crossbred dogs with high-grade MCT. Conclusion: The study finding has indicated that the level of Sox-2 expression may be a useful tumorigenic and prognostic biomarker because it correlates to the 2-tier grades but not dog breeds.

Cutaneous mast cell tumor in a captive Bush dog (Speothos venaticus): pathological and immunophenotypical aspects - case report

ABSTRACT A senile male captive bush dog (Speothos venaticus) presented a small perianal cutaneous nodule. Histologically, there was an ulcerated round cell tumor composed of well differentiated mast cells with abundant intracytoplasmic purple Giemsa-positive granules, with a diffuse eosinophilic infiltrate. Immunohistochemistry revealed that 30% of the neoplastic cells were positive for Kit in the cytoplasm and cell membrane, and all neoplastic cells were negative for MAC and CD3. Less than 10% of the neoplastic cells were positive for Ki67. At necropsy other primary tumors were identified in this animal, including an intestinal adenoma, an adrenal cortex adenoma and a testicular interstitial cell tumor.

Feline cystadenomatosis affecting the ears and skin of 57 cats (2011–2019)

Objectives This study aimed to understand epidemiological factors associated with feline cystadenomatosis, including signalment and papillomavirus PCR status. Cystadenomatosis is an uncommon condition primarily involving the ceruminous and apocrine skin and ear glands. Methods This was a retrospective case series. Clinical records from 2011 to 2019 from a tertiary referral hospital in Boston, MA, USA were screened for cases, and case data were re-evaluated and analyzed. The total patient pool contained 65,385 individual cats, of which 797 were referred to the dermatology service. Medical records and biopsy specimens were reviewed; the information collected included signalment, clinical signs, physical examination and diagnostic tests, comorbidities and histopathologic findings. PCR was performed on biopsy specimens to test for papillomavirus DNA. Results The cystadenomatosis population consisted of 57 cases (7.1% of total cases referred to the dermatology service) with 105 affected ears. Twenty-seven cases (48 ears) were confirmed via histopathology; four cats (7%) exhibited clinically cystic lesions on the periocular, periorbital and perianal regions; only one cat did not have pinnal lesions. Domestic shorthair cats were most often affected. Relative risk for cystadenomatosis was 2.24 times higher in male cats. In 48 cats (84.2%), ears were bilaterally affected. Seven cats (12.3%) had malignant neoplasia, which included: inflamed adenocarcinoma (n = 5); mast cell tumor (n = 1); or squamous cell carcinoma (n = 1). PCR testing on biopsy specimens from 24 cats revealed feline papillomavirus type 2 DNA in only four cats. Conclusions and relevance Cystadenomatosis was more prevalent in senior non-purebred cats, over-represented in male cats and did not appear to be associated with papillomavirus, feline infectious peritonitis, feline immunodeficiency virus/feline leukemia virus status or other identifiable illnesses. Further studies are needed to investigate the causes of cystadenomatosis.

Toceranib phosphate-associated nephrotic syndrome in a dog: a case report

Background Nephrotic syndrome (NS) is rare in dogs and is characterized by concurrent clinical findings of proteinuria, hyperlipidemia, hypoalbuminemia, and edema. NS has been reported in humans receiving tyrosine kinase inhibitors (TKI) and in dogs receiving masitinib. This is the first report of NS in a dog receiving toceranib phosphate. Case presentation An 8-year-old, female, spayed Labrador retriever was diagnosed with a 10 cm mast cell tumor on the left lateral abdomen. After completion of a 12-week vinblastine and prednisone protocol, she began treatment with toceranib phosphate (2.6 mg/kg by mouth, every other day). Proteinuria was documented prior to starting toceranib. On day 426 after diagnosis (day 328 of toceranib phosphate treatment), the dog was evaluated for diarrhea, lethargy and anorexia. On physical examination, dependent edema was noted on the ventral chest and abdomen, and sterile neutrophilic inflammation was aspirated from a 2.3 cm splenic nodule. The following laboratory values were reported: albumin < 1.5 g/dL; cholesterol 378 mg/dl and urine protein to creatinine ratio of 3.79. The patient was diagnosed with NS, and treatment with toceranib phosphate was discontinued. Low-dose aspirin was started in addition to an increased dosage of enalapril (0.47 mg/kg q12hr). No other therapy was instituted. The dog improved clinically, and laboratory values returned to near normal over the 8-week follow-up. She was euthanized 1399 days after discontinuing toceranib phosphate with progressive disease. Conclusions Nephrotic syndrome is a potential adverse event associated with the drug toceranib phosphate which may be reversible with discontinuation of treatment. Careful monitoring of urine protein, serum biochemistry, blood pressure and patient weight is advisable during treatment with toceranib phosphate.

Identification of common predisposing loci to hematopoietic cancers in four dog breeds

Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.

Review of Histological Grading Systems in Veterinary Medicine

Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement.

Occurrence of Cutaneous Neoplasia in Dogs with Actinic Dermatitis in a Veterinary Medical Teaching Hospital - UFRGS, Brazil

Background: Actinic dermatitis is an environmental skin disease resulting from excessive exposure to ultraviolet light irradiated by the sun. This phototoxic reaction affects dogs and cats, particularly with short hair and lightly pigmented skin, exposed to sun light. Primary lesions are typical from a sunburn and chronic exposure, and may induce to a premalignant lesion known as actinic keratosis, which may develop to neoplasms. The aim of the present study was to describe a retrospective study of actinic dermatitis and the occurrence of cutaneous neoplasia in dogs presented to a Veterinary Medical Teaching Hospital (HCV/UFRGS) in Porto Alegre, Rio Grande do Sul, Brazil in a period of 10 years.Materials, Methods & Results: A retrospective review of medical records from January 2009 to December 2019 was performed to identify dogs with actinic dermatitis. Twenty-eight dogs were diagnosed based on a history of sun exposure and skin lesions including erythema, scaling, comedones, thickened skin, hyperpigmentation, ulceration and/or secondary infections on poorly pigmented skin. In addition, in twelve dogs (42.8%) the disease was also confirmed by histopathology. Cutaneous lesions locations were previously defined as head, limbs, neck and trunk. The head was subdivided in chin, ears, face, lips and nasal plane; the limbs in pelvic and thoracic; and the trunk, in abdomen, dorsal pelvis, perianal and thorax. All 28 dogs diagnosed with actinic dermatitis in the study had been chronically exposed to solar radiation and had light skin and coat. Dogs were between 3 and 20 years old, mean 7.6 years and median 7 years, mostly female dogs (64.2%) and neutered or spayed (64.2%). The most affected breeds were American Pitbull Terrier (35.7%) and Boxers (28.5%). Other breeds were Bull Terrier, Dalmatian, Dogo Argentino and Scottish Terrier. In 15 cases, tumors were confirmed by cytopathology or histopathology, resulting in 9 different skin tumors and two types of cysts (epidermoid and follicular). Among these, the most prevalent malignant neoplasm was squamous cell carcinoma (66.7%), followed by mast cell tumor (40%), hemangiosarcoma (26.6%), and basal cell carcinoma (6.6%). Five benign tumors were identified: hemangioma (13.3%), fibroma (6.6%), lipoma (6.6%), sebaceous adenoma (6.6%) and trichoepithelioma (6.6%). The most prevalent location for actinic lesions was the trunk (92.8%), being more prevalent on the ventral abdomen (82.1%). Actinic lesions were also present on head, neck and limbs. In 13/15 patients (86.6%), actinic lesions and at least one neoplasia location matched.Discussion: Actinic dermatitis tends to occurs in mid-aged to senile dogs because of the disease progressive and chronic behavior and owners delay to detect early clinical signs. In fact, actinic dermatitis was diagnosed at the average age of 7.6 years in the present study. The skin lesions were mostly located on light hair areas and were not observed on pigmented skin. The trunk (mainly the abdomen) had higher frequency of skin lesions compared to other anatomic areas, possibly because some dogs like to sunbathe at dorsal or lateral recumbency, some floor types can reflect sunlight, and some ventral abdomen are hairless. Ultraviolet radiation causes important local and systemic immunogenic changes. The impairment of the immune system and antigen recognition can influence cutaneous susceptibility to develop neoplasm. In conclusion, approximately 50% of the dogs with actinic dermatitis were associated with different skin neoplasm. The most prevalent was squamous cell carcinoma, mast cell tumor and hemangiosarcoma. Actinic lesions and neoplasm matched location in almost all patients with both conditions, however it was not possible to define if solar radiation had predisposed the occurrence of all observed neoplasms. Further studies are needed to prove the influence of ultraviolet radiation in the development of different cutaneous neoplasms.