Isoliquiritigenin regulates the circ_0002860/miR-431-5p/RAB9A axis to function as a tumor inhibitor in melanoma

Background: Isoliquiritigenin (ISL) presents antitumor effects against melanoma cells. It is known that various circular RNAs (circRNAs) are involved in the development of melanoma. Therefore, the present study aims to investigate the molecular mechanisms of ISL and circ_0002860. Methods: Circ_0002860, microRNA-431-5p (miR-431-5p) and member RAS oncogene family (RAB9A) were detected through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Cell viability was examined via cell counting kit-8 assay. The proliferation ability was assessed using colony formation assay. Cell apoptosis and cell cycle were determined by flow cytometry. Transwell assay was used for detection of migration and invasion. Western blot was conducted for protein analysis. Target binding was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo research was performed through xenograft tumor assay. Results: Circ_0002860 was downregulated by ISL in melanoma cells. ISL-induced inhibitory effects on cell proliferation, cell cycle progression, migration and invasion were alleviated by circ_0002860 overexpression. MiR-431-5p was a target of circ_0002860. Circ_0002860 eliminated the ISL-induced tumor inhibition via sponging miR-431-5p in melanoma cells. Circ_0002860 elevated the RAB9A level by targeting miR-431-5p. The function of ISL was related to miR-431-5p/RAB9A axis in melanoma progression. Tumor growth was reduced by ISL in vivo through downregulating circ_0002860 to regulate miR-431-5p and RAB9A levels. Conclusion: The current data indicates that ISL suppressed cell malignant progression of melanoma via targeting the circ_0002860/miR-431-5p/RAB9A pathway.(AU)

Lesions of the oral cavity of dogs: 720 cases / Lesões da cavidade oral de cães: 720 casos

Seven hundred twenty cases of oral cavity lesions in dogs were diagnosed from 2015 to 2020 in Distrito Federal, Brazil. Four hundred thirty-two (60%) lesions were neoplastic, and 288 (40%) were non-neoplastic. Of the neoplasms, 229 (53%) were considered malignant and 203 (47%) benign, affecting mainly males, of 43 different breeds, with an average age of 9.4 years, mainly the gum and lip. Melanoma was the most (96/432, 22.2%) commonly diagnosed neoplasm, followed by peripheral odontogenic fibroma (68/432, 15.7%), papilloma (63/432, 14.5%) and squamous cell carcinoma (SCC) (56/432, 12.9%). Non-neoplastic lesions also affected males predominantly, from 41 different breeds, with an average age of 8.9 years, mainly in the gums, lip, and tongue. These lesions were diagnosed as inflammatory (230/288, 79.8%), hyperplastic (47/288, 16.3%) and other lesions (11/288, 3.8%).

Foram estudados 720 casos de lesões na cavidade oral em cães diagnosticados entre 2015 e 2020, no Distrito Federal. Dessas alterações, 432 (60%) foram neoplásicas e 288 (40%) não neoplásicas. Dentre os neoplasmas, 229 (53%) foram consideradas malignos e 203 (47%) benignos, acometendo principalmente machos, de 43 raças diferentes, com idade média 9,4 anos, afetando principalmente gengiva e lábio. Melanoma foi o neoplasma mais comumente diagnosticado (96/432; 22,2%), seguido do fibroma odontogênico periférico (68/432; 15,7%), papiloma (63/432; 14,5%) e carcinoma de células escamosas (56/432; 12,9%). As lesões não neoplásicas também acometeram predominantemente machos, de 41 raças diferentes, com idade média 8,9 anos, afetando principalmente gengiva, lábio e língua. Essas lesões foram diagnosticadas como inflamatórias (230/288; 79,8%), hiperplásicas (47/288; 16,3%) e como outras alterações (11/288; 3,8%).

Melanomas em cães no Sertão do Nordeste do Brasil - epidemiologia, fatores de risco e achados clinicopatológicos / Melanoma in dogs in the backlands of Northeastern Brazil - epidemiology, risk factors and clinicopathological findings

Background: Melanoma is a malignant neoplasm that arises from melanocytes and malanoblasts. It is also more frequently reported in dogs than in other species. They may arise from melanocytes in the skin, on the surfaces of the mucous membranes, and eyes. The aim of this study was to describe the epidemiological aspects, risk factors and clinicopathological findings of melanoma in dogs in the backlands, northeastern Brazil. Materials, Methods & Results: A retrospective study was carried out in all biopsy samples and necropsy examinations of dogs, from January 2003 to December 2021, at the Animal Pathology Laboratory of the Federal University of Campina Grande, Patos, Paraiba, northeastern Brazil. Epidemiological data, clinical signs, and gross lesions were reviewed from the diagnostic laboratory reports. Samples of the skin, lymph nodes, central nervous system and organs of the thoracic and abdominal cavities were fixed in 10% buffered formalin, processed routinely for histopathology, embedded in paraffin wax, cut into 4 µm sections, and stained with hematoxylin and eosin (HE). Histological sections were also submitted to immunohistochemistry with the primary antibody anti-Melan A. Of the 4717 records found, 1158 (24.5%) were diagnosed with neoplasms, of which 48 (4.14%) cases were of melanoma. Of this total, 28 (58.3%) dogs were elderly, 19 (39.6%) were adults, and 1 (2.1%) was young. Mixed breed animals were the most affected (42.6%), followed by the pinscher breed (19.1%). According to the anatomical region, the most affected site was the skin (38/53=71.7%), followed by the oral cavity (12/53=22.65%) and the eyes (3/53=5.7%). Grossly, the skin lesions were characterized by exophytic and usually blackened, sometimes irregular and firm, nodules. At cut, they had a smooth, compact and blackened surface. Lesions in the oral cavity were characterized by blackened, irregular and infiltrating nodules or masses. The ocular lesions were always unilateral and were characterized by an enlarged and diffusely blackened eyeball, with areas of ulceration and subversion of tissue architecture. In 5 animals there was more than one anatomical site affected, totaling 53 lesions. In 9 (17%) cases, metastases were identified, 8 in regional lymph nodes and 1 in the lung. Histopathology showed a densely non-encapsulated, poorly delimited, expansive and infiltrative neoplasm, composed of neoplastic cells arranged in islands or nests and supported by fibrovascular stroma, containing a variable amount of brownish pigment (melanin). Immunohistochemistry showed strong immunostaining of the neoplastic cells in brown by the anti-Melan A antibody. Discussion: The diagnosis of melanoma was established based on epidemiological, clinical, anatomopathological, and immunohistochemical findings. Gender is not a predisposing factor, and although there was no statistically significant relationship, males were more affected. Senescence is a conditioning risk factor. Elderly animals were more affected (P < 0.0001) than adult ones, with OR = 4.38; and young ones (P = 0.0051), with OR = 12.65. Some breeds, especially those with marked skin pigmentation, were more affected, however the most affected ones in this survey were pinscher and poodle. Cutaneous melanoma accounted for almost 72% of cases, contesting recent studies where oral cavity melanoma was more frequent. Therefore, it is believed that the climatic conditions of the backlands sub-region, in northeastern Brazil, associated with the individual characteristics of the dogs, are involved in the development of these neoplasms, since the climate is predominantly dry, with high temperatures throughout the year, with maximums that can reach 40ºC, favoring the exposure to high incidence of ultraviolet radiation.

Primary perianal malignant melanoma in a dog - combination therapy

Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM)has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thusthe prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment whichcombines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electricalpulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosedas perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs notedwere tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m2, intravenously), administered over 20min and cisplatin intratumorally (1 mg/cm3, equivalent to 1 mL/1cm3 total volume 20 mL) administered in the upper partsof the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses,(100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system,with tumor size of 5.0 x 5.0 cm (65.4 cm3). A second ECT session was performed with the same previous protocol, butwith a decreased dosage of carboplatin (240 mg/m2 consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then...

Primary perianal malignant melanoma in a dog - combination therapy

Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM)has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thusthe prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment whichcombines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electricalpulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosedas perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs notedwere tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m2, intravenously), administered over 20min and cisplatin intratumorally (1 mg/cm3, equivalent to 1 mL/1cm3 total volume 20 mL) administered in the upper partsof the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses,(100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system,with tumor size of 5.0 x 5.0 cm (65.4 cm3). A second ECT session was performed with the same previous protocol, butwith a decreased dosage of carboplatin (240 mg/m2 consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then...(AU)

Rare primary choroidal melanoma in a dog, with optic nerve infiltration / Raro melanoma primário de coroide em cão, com infiltração no nervo óptico

Intraocular melanocytic neoplasms are common in dogs. However, the choroidal location of these neoplasms and their infiltration into the optic nerve are unusual. This paper reports a case of primary choroidal melanoma in a 12-year-old male Dachshund. On the first examination, the animal presented left eye blepharospasm, protrusion of the nictitating membrane, conjunctival hyperemia, moderate congestion, hyphema, and intraocular hypertension. Opacity hindered the performance of fundoscopy in the affected eye. The ocular ultrasound examination revealed a cupuliform mass in the choroid. Due to suspected intraocular neoplasia, an exenteration was performed. Histopathological examination revealed primary choroidal melanoma with scleral and optic nerve invasion.(AU)

Neoplasias melanocíticas intraoculares são comuns em cães, contudo, a localização destas neoplasias na coroide e a infiltração delas no nervo óptico são pouco frequentes. O presente trabalho relata um caso de melanoma de coroide primário em um cão da raça Dachshund, com 12 anos de idade. O animal ao primeiro exame apresentou blefaropasmo no olho esquerdo, protrusão da terceira pálpebra, hiperemia conjuntival, congestão moderada, hifema e pressão intraocular elevada. Opacidade de meios transparentes impediu a realização de fundoscopia no olho acometido. O exame ultrassonográfico ocular revelou massa cupuliforme na coroide. Em razão da suspeita de neoplasia intraocular foi realizada exenteração. No exame histopatológico foi diagnosticado melanoma primário em coroide com invasão escleral e do nervo óptico.(AU)

Retrospective study of cutaneous neoplasms in horses treated at the Livestock Development Center of the Federal University of Bahia / Estudo retrospectivo das neoplasias cutâneas em equinos atendidos no Centro de Desenvolvimento da Pecuária da Universidade Federal da Bahia

The aim of this study was to determine the prevalence of cutaneous neoplasms in horses treated at the Center for the Development of Livestock at the Federal University of Bahia, as well as to correlate it with the coat color, breed, and age of the animal. For that, the attendance records for the last ten years were reviewed. When evaluating the files, 13 cases of cutaneous tumor in horses confirmed by histopathology and cytology were observed. The most prevalent skin tumors were sarcoid (38.5%), melanoma (23%), and fibrosarcoma (15.4%). Regarding the equine coat color, gray and sorrel horses were the most frequent with 30.7% and 23.1% of cases, respectively. As for the equine breed, the mangalarga marchador was the most prevalent (38.4%). Regarding age, 38.46% of the horses were up to 5 years old, 30.77% of the animals were between 4 and 10 years old, and 30.76% were between 11 and 16 years old. In the end, it can be concluded that sarcoid and melanoma were the most prevalent neoplasms.

Objetivou-se com este trabalho determinar a prevalência de neoplasias cutâneas em equinos atendidos no Centro de Desenvolvimento da Pecuária da Universidade Federal da Bahia, bem como correlaciona-la com a pelagem, raça e idade do animal. Para tanto revisou-se as fichas de atendimento dos últimos dez anos. Ao avaliar as fichas, observou-se 13 casos de tumor cutâneo em equinos confirmado por histopatologia ou citologia. Os tumores cutâneos mais prevalentes foram sarcoide (38,5%), melanoma (23%) e fibrossarcoma (15,4%). Com relação a pelagem, equinos tordilhos e alazões foram os mais frequentes com 30,7% e 23,1% dos casos, respectivamente. Quanto as raças, a mangalarga marchador foi a mais prevalente (38,4%). Em relação a idade, 38,46% dos equinos possuíam até 5 anos de idade, 30,77% dos animais apresentavam idade entre 4 e 10 anos e, 30,76% apresentavam idade entre 11 e 16 anos. Ao fim, pode-se concluir que o sarcoide e o melanoma foram as neoplasias mais prevalentes.

Pólipo fibroepitelial atípico em córnea de um cão Lhasa Apso / Atypical fibroepithelial polyp in the cornea of a Lhasa Apso dog

Background: Fibroepithelial polyps are benign tumors of mesenchymal and ectodermal origin. Regarding the localization related to the cutaneous region, they may affect the eyelid and periocular area. In veterinary medicine, polyps located in the urethra of dogs and monkeys, vagina of bitches and on the skin have been described. Fibroepithelial polyps may present as single to multiple nodules, exophytic to pedunculated, usually arising on a smooth surface of a common base. The aim of this paper is to describe the ocular and histopathological changes of a corneal fibroepithelial polyp of recurrent character in a dog. Case: A 20-year-old Lhasa Apso dog, with a history of progressive corneal neoformation in the right eye for 4 months. Patient was submitted to routine ophthalmic evaluation. At biomicroscopy, a discrete mucopurulent discharge was observed in the nasal corner, a nodule in the lower eyelid (± 3 mm), moderate conjunctival hyperemia, vascularization and corneal edema between 12 and 5 h, presence of a pinkish proliferative mass in 3 h, affecting the anterior stroma and opacity of the lens, Schirmer's Tear Test (STT) 20 mm/min and intraocular pressure (IOP) 10 mm/Hg. In the left eye, the STT and IOP were within normal range (17 mm/min and 11 mg/Hg, respectively) and at biomicroscopy only lens opacity was observed. Given the presence of the neoformation in the cornea, the patient underwent lamellar keratectomy to excise the mass and third eyelid flap. The tissue was then submitted to histopathology. The histopathological examination showed a proliferation of fibrous component with areas presenting reactive fibroblasts, with acidophilic cytoplasm and with little volume and slight neovascularization, presence of hyperplasia of the lining epithelium and cells with round to oval nuclei, with inconspicuous nucleoli, compatible with fibroepithelial polyp, without evidence of malignancy. After 18 months, the patient presented recurrence of the condition with a history of slow evolution (about ten months). The ophthalmic evaluation showed lesions very similar to the initial one, describing a recurrence of the lesion. Discussion: Corneal neoplasms are uncommon in dogs. The clinical findings in patients with ocular neoplasms include irregular to nodular masses, gray to reddish in color, and typically associated with a vascular supply. These features are related to the type of tumor and its degree of evolution. There are reports in the literature of ocular neoplasms such as squamous cell carcinoma, papilloma, melanocytoma, fibrosarcoma, hemangiosarcoma, melanoma, lymphoma. Related to fibroepithelial polyp with ocular involvement, there are rare reports in human literature and none in veterinary medicine. There is a human description of the presence of a polyp affecting the cornea associated with a corneal dermoid and e other cases of polyps of conjunctival origin. As far as treatment is concerned, the polyp should be surgically removed because of the possibility of recurrence, tissue metaplasia, or even transformation into a malignant tumor, as seen in the case reported here, in which even with surgical removal there was recurrence and metaplasia of the cells. Based on the histopathological findings, it can be concluded that this is a fibroepithelial polyp with a recidivating characteristic, not well described in the veterinary literature, with an atypical presentation affecting the cornea.

Solid iridociliary carcinoma in a dog

Background: Iridociliary epithelial tumors (ICETs) originate from the iris epithelium or ciliary body. They comprise ciliary body adenoma, carcinoma, pleomorphic adenocarcinomas, medulloepitheliomas, and other primitive neuroectodermal tumors. They are the second most common primary intraocular tumors in dogs and have already been reported in sheep and humans. In dogs, they occur more frequently in middle-aged to elderly animals, and the Labrador and Golden Retriever seem to be more predisposed breeds. This study aimed to describe the clinical and pathological aspects of solid iridociliary carcinoma in a dog. Case: A 3-year-old Poodle bitch was treated for discomfort in the left eyeball region, increased intraocular pressure and moderate buphthalmia. A direct ophthalmological examination was performed without equipment, and a mass was visualized in the posterior chamber, distorting the pupillary cleft. We opted for unilateral enucleation and forwarded the material for histological analysis. Macroscopically, the eyeball measured 3.4 cm (anteroposterior) x 2.6 cm (vertical), with a brownish mass that occupied the entire anterior chamber and part of the posterior chamber. Histologically, there was a neoformation in the ciliary body and iris pigment epithelium, partially well-delimited and densely cellular. The neoplasm was organized into predominantly solid formations interspersed with a discrete amount of blood vessels, rare bundles of fibrous stroma, and amorphous eosinophilic material forming membranes that were positive for PAS. Sections of the neoplasm were subjected to immunohistochemistry using anti-cytokeratin AE1/AE3, anti-S100 protein, anti-vimentin, and anti-Ki-67. Positive cytoplasmic immunostaining for cytokeratin and S-100 was observed. Only 45.6% of cells were positive for Ki-67 (500 cells). No immunostaining was observed for vimentin. Discussion: The diagnosis of solid iridociliary carcinoma was based on the histological features and positive immunostaining for cytokeratin AE1/AE3 and protein S100. Iridociliary carcinomas present positive immunostaining for cytokeratin, whereas adenomas and normal iridociliary epithelium do not present this immunostaining. Moreover, the high rate of cell proliferation was indicative of malignant neoplasia, as observed by the high mitotic count and high positivity for Ki-67. The S100 protein helped in the diagnosis of ICETs, as the iridociliary epithelium showed positive staining for this protein. Some histological features are important to consider in the diagnosis of iridociliary tumors in dogs, such as noninvasive growth in the posterior chamber, pigment epithelium, and thick homogeneous membranes on the cell surface. Furthermore, the presence of positive PAS membranes favors the diagnosis of iridociliary epithelial tumors. ICETs must be differentiated from melanocytomas, anterior uveal melanoma, medulloepitheliomas, and metastatic and pleomorphic carcinomas. The histological characteristics, especially the presence of PAS-positive membranes, associated with the immunohistochemical profile of neoplasm cells, help differentiate the ICETs from these tumors. In general, the prognosis is poor for eyeball and vision maintenance in canine iridociliary tumors, and scleral invasion is associated with a higher recurrence rate.

Metastatic melanoma in a Saanen goat: clinical, ultrasonographic and anatomopathological aspects - case report / [Melanoma metastático em cabra Saanen: aspectos clínicos, ultrassonográficos e Anatomopatológicos - relato de caso]

This report describes clinical, ultrasonographic and anatomopathological findings in a case of metastatic melanoma in an adult Saanen goat. Clinically, the goat had apathy, an intra-abdominal palpable firm structure, and exophytic keratinized areas on the skin of the udder. Ultrasound revealed non-encapsulated oval structures, with heterogeneous echogenicity and marked central and peripheral vascularization, and hypoechoic hepatic multifocal to coalescent areas. In the udder, there were non-encapsulated oval structures with heterogeneous echogenicity and hyperechoic center surrounded by hypoechogenic tissue. Grossly, there were black multifocal to coalescent areas in the liver, as well as black nodules in mammary and mesenteric lymph nodes, uterus, spleen, and myocardium. Microscopically, multifocal melanocytic neoplastic proliferation was observed in the dermis and junction of the udder epidermis. Most of the neoplastic cells had cytoplasmic granules of melanin. In the liver there were areas of neoplastic tissue compressing the adjacent parenchyma, with central foci of necrosis, mild desmoplasia, and multifocal infiltration of malignant cells into the adjacent tissues. Similar findings were observed in the mammary and mesenteric lymph nodes, uterus, spleen, and myocardium, which characterized metastatic melanoma. Ultrasonography played a key role for establishing the diagnosis of a metastatic melanoma and helped establish a proper clinical management protocol.(AU)

Este relato descreve os achados clínicos, ultrassonográficos e anatomopatológicos em um caso de melanoma metastático em uma cabra Saanen adulta. Clinicamente, a cabra apresentava apatia, estrutura firme palpável intra-abdominal e áreas exofíticas queratinizadas na pele do úbere. A ultrassonografia revelou estruturas ovais não encapsuladas, com ecogenicidade heterogênea e marcada vascularização central e periférica, além de áreas hepáticas multifocais a coalescentes hipoecoicas. No úbere, havia estruturas ovais não encapsuladas, com ecogenicidade heterogênea e centro hiperecogênico circundado por tecido hipoecogênico. Macroscopicamente, havia áreas pretas multifocais a coalescentes no fígado, bem como nódulos pretos nos linfonodos mamários e mesentéricos, no útero, no baço e no miocárdio; microscopicamente, proliferação neoplásica melanocítica multifocal foi observada na derme e na junção da epiderme do úbere. A maioria das células neoplásicas apresentava grânulos citoplasmáticos de melanina. No fígado, havia áreas de tecido neoplásico comprimindo o parênquima adjacente, com focos centrais de necrose, desmoplasia leve e infiltração multifocal de células malignas nos tecidos adjacentes. Achados semelhantes foram observados nos nódulos linfáticos mamários e mesentéricos, no útero, no baço e no miocárdio, que caracterizaram o melanoma metastático. A ultrassonografia desempenhou um papel fundamental para estipular o diagnóstico de um melanoma metastático e ajudou a estabelecer um protocolo de manejo clínico adequado.(AU)

Diffuse melanosis secondary to metastatic melanoma in a Nelore bull

Relatamos um caso de melanose difusa secundária a melanoma maligno metastático em um touro Nelore. Os sinais clínicos incluíram isolamento do rebanho, epistaxe, hipertermia, pálidas membranas oculares, diarreia mucóide e urina escura. Apesar da terapia antiinflamatória e antibiótica, o touro morreu 45 dias após o início dos sinais clínicos. A lesão mais marcante foi uma descoloração negra difusa para os órgãos viscerais, incluindo fígado, baço, pulmões, nódulos linfáticos e rins; todos esses órgãos afetivos foram moderadamente aumentados ”. A urina estava preta. Histologicamente, 50-80% do parênquima do fígado, baço e linfonodos foi obliterado por agregados de melanócitos neoplásicos carregados de melanina. Essas células neoplásicas também ocorreram nos capilares do fígado, baço, linfonodos, bexiga urinária, pulmões e rins. A imunohistoquímica de melanócitos neoplásicos foi positiva para os marcadores Melan A e PNL2. Pigmento marrom a preto abundante foi encontrado em melanófagos nos pulmões, confirmado por imunohistoquímica com IBA1.

Diffuse melanosis secondary to metastatic melanoma in a Nelore bull

Relatamos um caso de melanose difusa secundária a melanoma maligno metastático em um touro Nelore. Os sinais clínicos incluíram isolamento do rebanho, epistaxe, hipertermia, pálidas membranas oculares, diarreia mucóide e urina escura. Apesar da terapia antiinflamatória e antibiótica, o touro morreu 45 dias após o início dos sinais clínicos. A lesão mais marcante foi uma descoloração negra difusa para os órgãos viscerais, incluindo fígado, baço, pulmões, nódulos linfáticos e rins; todos esses órgãos afetivos foram moderadamente aumentados ”. A urina estava preta. Histologicamente, 50-80% do parênquima do fígado, baço e linfonodos foi obliterado por agregados de melanócitos neoplásicos carregados de melanina. Essas células neoplásicas também ocorreram nos capilares do fígado, baço, linfonodos, bexiga urinária, pulmões e rins. A imunohistoquímica de melanócitos neoplásicos foi positiva para os marcadores Melan A e PNL2. Pigmento marrom a preto abundante foi encontrado em melanófagos nos pulmões, confirmado por imunohistoquímica com IBA1.(AU)

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 ofdeath. Adjuvant therapy should be recommended because of potential recurrence and metastasis. Oral melanoma has a poorprognosis even when adjuvant treatments are used. There are some treatment options, but the high death rate due to thedisease is still a challenge. The aim of this study was to assess the overall survival of dogs diagnosed with oral melanomaand treated with adjuvant chemotherapy and immunotherapy.Materials, Methods & Results: A retrospective analysis was carried out in 20 dogs with oral melanocytic or amelanocyticmelanomas. Cases were staged according to a modified World Health Organization clinical staging system for canine oralmalignant 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 dividedinto 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 confirmedwith histopathological exam and immunohistochemistry (IHC) when necessary. In poorly differentiated neoplasms, IHC wasperformed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Animals were dividedinto 2 groups: dogs submitted to surgery alone were included in group 1 (G1); dogs submitted...

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 ofdeath. Adjuvant therapy should be recommended because of potential recurrence and metastasis. Oral melanoma has a poorprognosis even when adjuvant treatments are used. There are some treatment options, but the high death rate due to thedisease is still a challenge. The aim of this study was to assess the overall survival of dogs diagnosed with oral melanomaand treated with adjuvant chemotherapy and immunotherapy.Materials, Methods & Results: A retrospective analysis was carried out in 20 dogs with oral melanocytic or amelanocyticmelanomas. Cases were staged according to a modified World Health Organization clinical staging system for canine oralmalignant melanoma. Tumor size (T1: < 2 cm; T2: 2 - 4 cm; T3: > 4 cm), regional metastasis (N0: no metastasis; N1:metastasis) and presence of distant metastasis (M0: no metastasis; M1: metastasis) are evaluated. Then, cases were dividedinto 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 confirmedwith histopathological exam and immunohistochemistry (IHC) when necessary. In poorly differentiated neoplasms, IHC wasperformed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Animals were dividedinto 2 groups: dogs submitted to surgery alone were included in group 1 (G1); dogs submitted...(AU)

Use of Giemsa staining for the immunohistochemical counterstaining in canine melanomas: an "old and forgotten" method

Melanoma is a neoplasm originating from melanocytes and represents 7% of skin tumors and the most common in oral cavity of dogs. Melanoma may present melanocytic pigment in its cytoplasm in varying quantity and its characterization by immunohistochemistry (IHC) is challenging due to the use of chromogen diaminobenzidine (DAB) which itself produces a brown product what makes difficult to distinguish from melanin pigment in this technique. To demonstrate a reliable technique, the use of the Giemsa counterstaining was performed in the IHC of melanomas with different degrees of pigmentation for different cytoplasmic, membrane and nuclear markers. The modification in the IHC technique by the counterstaining of Giemsa allows observable differences under the microscope between melanic pigment(in a blue-green stain), while the DAB chromogen will be observed in brown. With this technique, the prognostic and predictive interpretation of markers in canine melanomas may be more reliable in definitions of clinical behaviors and inexperimental analyzes.(AU)

Use of Giemsa staining for the immunohistochemical counterstaining in canine melanomas: an "old and forgotten" method

Melanoma is a neoplasm originating from melanocytes and represents 7% of skin tumors and the most common in oral cavity of dogs. Melanoma may present melanocytic pigment in its cytoplasm in varying quantity and its characterization by immunohistochemistry (IHC) is challenging due to the use of chromogen diaminobenzidine (DAB) which itself produces a brown product what makes difficult to distinguish from melanin pigment in this technique. To demonstrate a reliable technique, the use of the Giemsa counterstaining was performed in the IHC of melanomas with different degrees of pigmentation for different cytoplasmic, membrane and nuclear markers. The modification in the IHC technique by the counterstaining of Giemsa allows observable differences under the microscope between melanic pigment(in a blue-green stain), while the DAB chromogen will be observed in brown. With this technique, the prognostic and predictive interpretation of markers in canine melanomas may be more reliable in definitions of clinical behaviors and inexperimental analyzes.

Cutaneous metastatic melanoma in a Siberian tiger (Panthera tigris altaica) - case report / Melanoma cutâneo metastático em um tigre-siberiano (Panthera tigris altaica) - relato de caso

A male 15-year-old captive Siberian tiger (Panthera tigris altaica) developed pelvic limb hypermetry over the past 10 years. Recently, an ulcerated black nodule located caudally to the right ear was observed. The animal was submitted to surgery for removing the tumor, but died during anesthetic recovery. At necropsy, another infiltrative nodule was observed caudally to the right ear. Histologically, both nodules corresponded to melanocytic neoplasia, varying from heavily pigmented to amelanotic, with metastasis to mediastinal lymph nodes, spleen and lung. Lipofuscinosis and corpora amylacea were histologically observed in the central nervous system. Macroscopic and histologic findings confirmed the diagnosis of skin metastatic melanoma in a captive adult Siberian tiger.(AU)

Um tigre-siberiano (Panthera tigris altaica) de cativeiro, macho, de 15 anos de idade, apresentou hipermetria dos membros pélvicos nos últimos 10 anos, e recentemente, foi observado um nódulo preto e ulcerado caudalmente à orelha direita. O animal foi submetido à cirurgia para remoção do nódulo e morreu durante a recuperação anestésica. À necropsia, outro nódulo infiltrativo, foi detectado caudalmente a orelha direita. Histologicamente, ambos os nódulos correspondiam à neoplasia melanocítica, com células variando de fortemente pigmentadas a amelanóticas, com metástase para linfonodos mediastinais, baço e pulmão. Havia lipofucsinose e corpora amilácea no sistema nervoso central. Os achados macroscópicos e histológicos confirmam o diagnóstico de melanoma cutâneo metastático em um tigre-siberiano adulto de cativeiro.(AU)

Cutaneous metastatic melanoma in a Siberian tiger (Panthera tigris altaica) - case report / Melanoma cutâneo metastático em um tigre-siberiano (Panthera tigris altaica) - relato de caso

A male 15-year-old captive Siberian tiger (Panthera tigris altaica) developed pelvic limb hypermetry over the past 10 years. Recently, an ulcerated black nodule located caudally to the right ear was observed. The animal was submitted to surgery for removing the tumor, but died during anesthetic recovery. At necropsy, another infiltrative nodule was observed caudally to the right ear. Histologically, both nodules corresponded to melanocytic neoplasia, varying from heavily pigmented to amelanotic, with metastasis to mediastinal lymph nodes, spleen and lung. Lipofuscinosis and corpora amylacea were histologically observed in the central nervous system. Macroscopic and histologic findings confirmed the diagnosis of skin metastatic melanoma in a captive adult Siberian tiger.(AU)

Um tigre-siberiano (Panthera tigris altaica) de cativeiro, macho, de 15 anos de idade, apresentou hipermetria dos membros pélvicos nos últimos 10 anos, e recentemente, foi observado um nódulo preto e ulcerado caudalmente à orelha direita. O animal foi submetido à cirurgia para remoção do nódulo e morreu durante a recuperação anestésica. À necropsia, outro nódulo infiltrativo, foi detectado caudalmente a orelha direita. Histologicamente, ambos os nódulos correspondiam à neoplasia melanocítica, com células variando de fortemente pigmentadas a amelanóticas, com metástase para linfonodos mediastinais, baço e pulmão. Havia lipofucsinose e corpora amilácea no sistema nervoso central. Os achados macroscópicos e histológicos confirmam o diagnóstico de melanoma cutâneo metastático em um tigre-siberiano adulto de cativeiro.(AU)

Treatment of limbal melanocytoma with full excision and a fresh homologous corneoscleral graft in a dog

Background: Limbal melanoma has been diagnosed in dogs and due to progression may cause vision loss and eyeballremoval. Definitive diagnosis is made through histopathological examination. Therapeutic options include full thicknessresection and repair by homologous corneal tissue, synthetic graft material, and enucleation. In this report, we describe acase of limbal melanocitoma in a dog that has been treated successfully with fresh homologous corneoscleral graft.Case: A 5-year-old female Labrador was referred to the Ophthalmology Veterinary Section of the Federal University ofRio Grande do Sul (UFRGS), Porto Alegre, Brazil, with a history of a pigmented mass located on the left eye. Ophthalmicexamination revealed a pigmented mass located at the left temporal limbus with corneal involvement. Surgical excisionfollowed by reconstruction using fresh homologous corneoscleral was recommended. The patient was premedicated withacepromazine (0.05 mg/kg, IM) and meperidine (20 mg/kg, IM). Anaesthesia was induced with propofol (10 mg/kg, IV)and maintained with isoflurane. Atracurium (0.2 mg/kg, IV) was administered to maintain a central eye position. The massand a free margin were removed by full-thickness corneoscleral resection. A corneoscleral graft was harvested from a dogthat had been euthanised for reasons unrelated to this study and sutured with 9-0 polyglactin 910 using a simple interruptedpattern. The mass was immediately fixed in 10% neutral buffered formalin and submitted for histological sectioning androutine staining. Based on the histopathological analysis it was confirmed limbal melanocytoma. Postoperative treatmentconsisted...

Treatment of limbal melanocytoma with full excision and a fresh homologous corneoscleral graft in a dog

Background: Limbal melanoma has been diagnosed in dogs and due to progression may cause vision loss and eyeballremoval. Definitive diagnosis is made through histopathological examination. Therapeutic options include full thicknessresection and repair by homologous corneal tissue, synthetic graft material, and enucleation. In this report, we describe acase of limbal melanocitoma in a dog that has been treated successfully with fresh homologous corneoscleral graft.Case: A 5-year-old female Labrador was referred to the Ophthalmology Veterinary Section of the Federal University ofRio Grande do Sul (UFRGS), Porto Alegre, Brazil, with a history of a pigmented mass located on the left eye. Ophthalmicexamination revealed a pigmented mass located at the left temporal limbus with corneal involvement. Surgical excisionfollowed by reconstruction using fresh homologous corneoscleral was recommended. The patient was premedicated withacepromazine (0.05 mg/kg, IM) and meperidine (20 mg/kg, IM). Anaesthesia was induced with propofol (10 mg/kg, IV)and maintained with isoflurane. Atracurium (0.2 mg/kg, IV) was administered to maintain a central eye position. The massand a free margin were removed by full-thickness corneoscleral resection. A corneoscleral graft was harvested from a dogthat had been euthanised for reasons unrelated to this study and sutured with 9-0 polyglactin 910 using a simple interruptedpattern. The mass was immediately fixed in 10% neutral buffered formalin and submitted for histological sectioning androutine staining. Based on the histopathological analysis it was confirmed limbal melanocytoma. Postoperative treatmentconsisted...(AU)