Treatment of Canine Oral Melanoma with Adjuvant Chemotherapy and Immunotherapy

Background: Melanoma is the most frequent cancer in the canine oral cavity. It shows an aggressive behavior, characterized by rapid and invasive growth and high metastatic potential. Metastasis is seen in more than 80% of dogs at time of death. Adjuvant therapy should be recommended because of potential recurrence and metastasis. Oral melanoma has a poor prognosis even when adjuvant treatments are used. There are some treatment options, but the high death rate due to the disease is still a challenge. The aim of this study was to assess the overall survival of dogs diagnosed with oral melanoma and treated with adjuvant chemotherapy and immunotherapy. Materials, Methods & Results:A retrospective analysis was carried out in 20 dogs with oral melanocytic or amelanocytic melanomas. Cases were staged according to a modified World Health Organization clinical staging system for canine oral malignant melanoma. Tumor size (T1: 4 cm), regional metastasis (N0: no metastasis; N1: metastasis) and presence of distant metastasis (M0: no metastasis; M1: metastasis) are evaluated. Then, cases were divided into 4 stages: I (T1 N0 M0), II (T2 N0 M0), III (T3 N0-1 M0, Tx N1 M0) and IV (Tx Nx M1). Diagnoses were confirmed with histopathological exam and immunohistochemistry (IHC) when necessary. In poorly differentiated neoplasms, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Animals were divided into 2 groups: dogs submitted to surgery alone were included in group 1 (G1); dogs submitted to surgery associated with adjuvant chemotherapy with four 21-day cycles of carboplatin (300 mg/m2) and immunotherapy with six 7-day cycles of interferon-α (3 x 106 IU/m2) were included in group 2 (G2). Twenty dogs diagnosed with oral melanoma were evaluated: 3 were included in G1 and 17 in G2. Considering clinical staging of the dogs: 7 stage II, 12 stage III and only 1 stage IV. There was no stage I patients. In poorly differentiated neoplasias, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Patient follow-up was obtained through the evaluation of patient records and telephone interviews with owners. The overall survival time (OS) was defined by the period (in days) between the date of surgical excision and the death caused by the disease. Median overall survival time was 86 days for animals in G1 and 894 days for animals in G2 (P = 0.01). Discussion: Carboplatin was considered an appropriate cytostatic drug to treat microscopic disease in oral melanoma. INF-α was chosen for immunotherapy in this study because it promotes immune system stimulation associated with an indirect antiproliferative effect on neoplastic cells. The association of INF-α and carboplatin resulted in a significant increase in overall survival, when compared to the literature, suggesting that association of chemotherapy and immunomodulation is an important strategy in the treatment of canine oral melanoma. Controlled prospective randomized trials are necessary to confirm the benefits of chemotherapy and immunotherapy association to treat canine oral melanoma. Adjuvant therapy with chemotherapy and immunotherapy was considered effective to increase overall survival and maintained quality of life of dogs diagnosed with oral melanoma

Histomorphological and Immunophenotypic Characterization of Feline Injection Site-Associated Sarcoma

Background: Feline Injection Site-Associated Sarcoma (FISS) is a mesenchymal neoplasia of aggressive behavior that develops in sites where vaccine or drugs were administered. FISS is clinically characterized by the appearance of a solitary firm nodule or a diffuse mass, adhered to tissues, in regions associated to vaccine or drug applications. Despite low prevalence, tumor recurrence rates can reach 80%. FISS present more aggressive histological characteristics when compared to sarcomas not associated to injection sites. The aim of this paper is to contribute towards the understanding of the biological behavior of FISS.Materials, Methods & Results: Sixteen samples of FISS were analyzed. Fibrosarcomas were the most frequent histological subtype (62.5%). Malignant peripheral nerve sheath tumor was diagnosed in 18.75% cases. Ten (62.5%) FISS were classified as grade II; 4/16 (25%) grade I, and 2/16 (12.5%) grade III. Cox-2 overexpression occurred in 3/16 (18.75%) samples, with positive correlation between Cox-2 expression and cellularity (r = 0.696, P = 0.003). Mitotic index lower than 9 events was found in 11/16 (68.7%) samples and between 10 and 19 mitotic events in 5/16 (31.3%) cases. Mean Ki-67 expression was 2.39 ± 2.48%. FISS characterized as fibrosarcomas presented longer overall survival (median 545 days) than other histological subtypes (median 130.5 days) [P = 0.01].Discussion: Patients with FISS generally present with larger nodules than those with sarcomas not associated to injections, suggesting a challenge for pet owners to note subcutaneous tumors in the interscapular region, in addition to the aggressive biological behavior of FISS. The influence of size on prognosis remains controversial. An association between histologic grade and the development of metastasis has been observed, with patients with grade III FISS associated with an increase in the metastatic rate. The present study did not find a correlation between overall survival and histologic grade. A positive correlation between the presence of giant multinucleated cells and tumor grade has been observed.Despite the absence of such correlation in the present study, possibly due to a small sample, a trend for higher frequency of giant cells in advanced histologic grade was observed. Cox-2 expression in 81.75% and overexpression in 18.75% of our samples contrasts with the 64% Cox-2 expression and the absence of Cox-2 expression found by other authors. A positive moderate correlation between cellularity and Cox-2 expression was also observed, while another study did not find a correlation of Cox-2 expression with tumor grade, recurrence rates or overall survival. Cox metabolites such as prostaglandins can enhance cellular proliferation, inhibit apoptosis, induce angiogenesis, alter cellular adherence to facilitate metastatic development and inhibit immune surveillance. In the present study, no correlation was found between Cox-2 and angiogenesis in FISS. Our findings demonstrated low immunolabeling for Ki-67. A previous study analyzed 52 samples of FISS, 51% of them considered grade III, with a mean Ki-67 labeling of 14%. The lower Ki-67 staining in the samples of the present study may be related to the lower number of samples of grade III FISS or to a difference in the studied population. Fibrosarcomas are associated with better prognosis than other histological subtypes. Furthermore, malignant peripheral nerve sheath tumors were diagnosed as a possible histological subtype of FISS

Focal Peripheral Neuropathy Associated with Lymphoma in Dogs

Background: Peripheral neuropathies result in sensory, motor or autonomic dysfunctions due to impairment of peripheral spinal or cranial nerves. Neoplasms such as lymphoma are cited as one of the many aetiological causes and it may affect the nerve directly, by compression, or indirectly, or paraneoplastic, by remote action of the neoplasm located in an extra-neural site. This study aimed to report two cases of cranial nerve neuropathy (trigeminal and facial) associated with canine lymphoma, contributing to a better understanding of its paraneoplastic effects on the nervous system, as well as the diagnosis and treatment of these conditions.Cases: Two cases of canine lymphoma associated with possible signs of paraneoplastic peripheral neuropathy were attended at the Veterinary Hospital from the Universidade Federal de Minas Gerais (HV UFMG). Case 1. A spayed mixed breed bitch, with lethargy and unilateral exophthalmos. Brain computed tomography revealed a retrobulbar mass and cytology was diagnostic for extranodal lymphoma. Subsequent to computed tomography, the dog was presented with hypotrophy of the facial musculature and difficulty in grasping food, consistent with trigeminal nerve palsy, which resolved after institution of the 19-week chemotherapy protocol from the University of Wisconsin. Nevertheless, disease reccurred and a rescue protocol was initiated. Case 2. A female Dalmatian, spayed, was diagnosed with multicentric lymphoma, after cytology of the left mandibular lymph node. Chemotherapy was initiated with the same protocol of the previous case. However, the disease progressed and it was observed facial asymmetry with ptosis of the left eyelid, pina and lips, in addition to difficulty in grasping food, suggesting facial and trigeminal cranial nerve palsy. Clinical signs resolved after institution of a rescue chemotherapy protocol. However, in both cases, disease progression and poor clinical condition resulted in decision of euthanasia and necropsy was not authorized.Discussion: Canine lymphoma is often associated with paraneoplastic syndromes, with neuropathy being one of its possible clinical manifestations. In spite of that its pathogenesis remains unclear, with little information in the veterinary literature. Diagnosis is challenging and must be initially based on recognition of neurological clinical signs and lesion localization, as in the reported cases with lesions located on the fifth and seventh cranial nerves. In the patient from the first case, the absence of clinical signs and laboratory abnormalities suggestive of endocrinopathies, associated with neurological signs restricted to the trigeminal nerve, bilaterally, before starting chemotherapy and without the identification of brain lesions in computed tomography, suggested paraneoplastic involvement as the cause of neuropathy. In the second case described, the absence of clinical signs and laboratory abnormalitiess suggestive of endocrinopathies or nutritional deficiencies, associated with neurological signs restricted to the facial and trigeminal cranial nerves, suggested direct or indirect tumour involvement. Both cases showed improvement of neurological clinical signs after chemotherapy which favored the therapeutic diagnosis. Nevertheless, failure to authorize necropsy of patients made it impossible to confirm that peripheral neuropathy is secondary to the remote effect of lymphoma

Consensus for the diagnosis, prognosis and treatment of feline mammary tumors

Mammary neoplasms are described as the third most common type of feline tumor, after haematopoietic and skin tumors, and present a challenge for clinicians because the prognosis for feline mammary tumors ranges from guarded to poor. Thus, it is necessary to define new therapeutic approaches and establish more in-depth knowledge about this disease in felines. The main aspects of the diagnosis, prognosis and treatment of feline mammary neoplasia were discussed, aiming to standardize the criteria and to serve as a guide for pathologists and veterinary clinicians.As neoplasias mamárias são descritas como o terceiro tipo mais frequente de tumor em felinos (após as neoplasias hematopoiéticas e cutâneas) e apresentam um desafio para os clínicos devido ao prognóstico, que varia de reservado a ruim. Assim, é necessário conhecer melhor essa doença em felinos e definir novas abordagens terapêuticas. Discutiu-se os principais aspectos de diagnóstico, prognóstico e tratamento da neoplasia mamária felina, com o objetivo de padronizar os critérios e servir de guia para patologistas e clínicos veterinários

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors

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

Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin) on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes) are required for definitive diagnosis of round cell tumours in dogs

Use of surgery and carboplatin in feline malignant mammary gland neoplasms with advanced clinical staging

Background/Aim: Feline mammary carcinomas (FMCs) are characterized by poor prognosis and little progress has been made in extending patient survival. The aim of the study was to compare overall survival periods of FMCs submitted to different treatment protocols, including surgery and adjuvant chemotherapy. Materials and Methods: Analysis of conventional surgical excision alone or in association with adjuvant chemotherapy with carboplatin in sixteen cats diagnosed with stage III and grade II or III FMCs was performed. Results: Patients treated with surgery and chemotherapy presented a longer overall survival (OS) than those treated only with surgery, however, no statistical difference was observed when comparing both treatments (p=0.883). Conclusion: Therapeutic benefit of carboplatin remains invalidated for FMCs and further investigation regarding adjuvant therapies are warranted. Surgery remains as the gold treatment in FMCs.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES