Mast cell tumors (MCTs) are hematopoietic neoplasms composed of mast cells. It is highly common in dogs and is extremely important in the veterinary oncology field. It represents the third most common tumor subtype, and is the most common malignant skin tumor in dogs, corresponding to 11% of skin cancer cases. The objective of this critical review was to present the report of the 2nd Consensus meeting on the Diagnosis, Prognosis, and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors, which was organized by the Brazilian Association of Veterinary Oncology (ABROVET) in August 2021. The most recent information on cutaneous and subcutaneous mast cell tumors in dogs is presented and discussed.

Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.

Background: The antibody Ki-67 is a reliable and easy tool to accurately assess the growth fraction of neoplasms in humans and animals, and it has been used to predict the clinical outcome. Therefore, the aim of the present study was to investigate the immunohistochemical expression pattern of Ki-67 in normal and neoplastic perianal glands of dogs to evaluate the possible use of this proliferation marker as an ancillary method of perianal tumor diagnosis. We studied 42 cases of perianal gland neoplasms including adenomas (n = 15), epitheliomas (n = 15), and carcinomas (n = 12). As controls, 13 tissue samples from normal perianal glands were used. A Ki-67 index was established by a computer-assisted image analysis and compared with manual counting. Results: Out of the 42 cases of perianal gland neoplasms, 34 were from males and eight from females. Recurrence was reported in 14 cases, being higher (8/12) in carcinomas. Immunostaining for Ki-67 revealed that the carcinomas showed a higher proliferation rate (9.87%) compared to groups of epitheliomas (2.66%) and adenomas (0.36%). For adenomas and epitheliomas of the perianal glands the computer-assisted counting and the manual counting gave similar results; however, only the computer-assisted image analysis was efficient to predict the perianal gland carcinoma recurrence. Conclusion: Since there were significant differences in the number of Ki-67-positive nuclei, this marker proved to be effective in helping the classification of perianal gland neoplasms and to refine the diagnosis criteria, especially in those samples with high variation in morphology/area. Also, higher Ki-67 index is related to recurrence in cases of perianal gland carcinomas. Further, the computer-assisted image analysis proved to be a fast and reliable method to assess the Ki-67 index in perianal gland neoplasms.

Avaliação da caspase-3 e Ki-67 como marcadores prognósticos nas neoplasias mamárias em cadelas

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time.

The immunophenotype is regarded as an independent prognostic factor in high-grade lymphomas, seeing that lymphomas of T-cell origin are associated with shorter survival time. Although a number of studies have evaluated the immunophenotypical profile of lymphoma in the USA and Europe, Brazilian research on the matter remains scarce. Exact characterization of the histopathological type is crucial to establish proper treatment and prognosis. This study evaluated the database of immunohistochemistry laboratories that perform immunophenotyping of canine lymphoma in Brazil. A total of 203 cases of multicentric lymphoma were classified according to the WHO classification. Immunophenotyping was able to identify 71.4% lymphomas of B-cell line, 27.1% of T-cell line and 1.5% of non-B cells and non-T cell lines. Diffuse large B-cell lymphoma was the most common with 59.1% of the cases. Among T-cell lymphomas, lymphoblastic was the most common (11.33% of the cases). Even though canine lymphomas tend to be high-grade, indolent lymphomas comprised 11.82% of the cases and T-zone lymphoma was the most prevalent (8.86%). The immunophenotype of multicentric lymphoma in Brazil is similar to those in other parts of the world, which suggests similar etiologic factors to the development of this disease.