Denner Santos dos Anjos

Case summary: An 11-year-old, neutered male domestic shorthair cat was referred for diabetes mellitus and recurrent episodes of respiratory distress. Physical examination identified an abdominal mass, while routine laboratory testing was unremarkable. Cardiac evaluation revealed cardiomyopathy with a hypertrophic phenotype. Thoracic and abdominal CT identified a heterogeneous mass (5.6 cm) in the right caudal abdominal region, with normal-appearing adrenal glands. Urinary normetanephrine:creatinine and metanephrine:creatinine ratios were markedly increased (3164 µg/g and 271 µg/g, respectively), representing 51-fold and 15-fold increases compared with 13 clinically healthy control cats, strongly supporting the suspicion of a functional extra-adrenal paraganglioma. After phenoxybenzamine treatment, exploratory laparotomy was performed. Due to cardiovascular instability characterized by tachycardia and hypertension, tumor resection was not feasible; however, incisional biopsy samples were successfully obtained. Immunohistochemical findings confirmed the diagnosis of a neuroendocrine tumor, with immunoreactivity for chromogranin A and neuron-specific enolase. The absence of immunoreactivity for pan-cytokeratin (AE1/AE3) and the presence of S100 protein staining in sustentacular cells were consistent with an extra-adrenal paraganglioma. This is the first reported functional extra-adrenal paraganglioma in a cat with biochemical confirmation of catecholamine excess based on urinary normetanephrine:creatinine and metanephrine:creatinine ratios. Relevance and novel information: This case highlights the diagnostic utility of urinary metanephrines as a non-invasive tool for detecting catecholamine excess in cats. It also underscores the importance of considering paraganglioma in cats with episodic respiratory distress, hypertrophic phenotype cardiomyopathy, and the presence of an extra-adrenal mass.

Multilobular Bone Tumor (MBT) is a rare, slow-growing, and locally invasive neoplasm in middle-aged to older dogs, occurring predominantly in flat bones of the skull, pelvis, or ribs. This work reports the case of a 10-year-old, castrated, male Schnauzer, presenting with a tumorous growth in the incisor region measuring 1.0 x 0.7 x 0.6 centimeters for 30 days. Excisional biopsy revealed polygonal, hyperchromatic mesenchymal cells with oval nuclei and condensed chromatin, confirming a well-differentiated MLTB. However, the tumor recurred within 5 months, measuring 3.3 x 2.4 centimeters in the same region. Computed tomography (CT) revealed a mixed bone reaction, predominantly lytic, involving the incisive bone at the level of the incisor and canine teeth. The owner declined rostral maxillectomy and opted for a palliative approach with electrochemotherapy (bleomycin 15,000 UI/m2) at the tumor site. Complete remission was achieved within 28 days with macroscopic areas suggestive of scarring. The disease-free interval was 365 days without adjuvant therapy. However, at 435 days post-procedure (D0), recurrence was observed in the incisor region, accompanied by respiratory distress. Staging revealed pulmonary metastasis, leading to a decision for humane euthanasia owing to poor prognosis. Electrochemotherapy for oral MLTB in this dog demonstrated good efficacy, prolonged local control, and no regional functional impairments. O Tumor Ósseo Multilobular (MLTB) é um tumor raro, de crescimento lento e localmente invasivo em cães de meia idade a idosos, ocorrendo principalmente em ossos chatos do crânio , pelve ou costela.. Esse trabalho relata um macho, castrado, raça Schnauzer, de 10 anos de idade, com crescimento tumoral na região dos incisivos de 1,0 x 0,7 x 0,6 centímetros há 30 dias. A biópsia excisional foi realizada evidenciando células mesenquimais poligonais, hipercromática, núcleo oval, cromatina condensada confirmando MLTB bem diferenciado. Entretanto, houve recidiva em 5 meses de 3,3 x 2,4 centímetros na mesma região. A tomografia computadorizada evidenciou reação óssea mista, predominantemente lítica, envolvendo osso incisivo ao nível de dentes incisivos e caninos. A maxilectomia rostral foi recusada pelo tutor, optando pela abordagem paliativa com eletroquimioterapia (bleomicina 15,000 UI/m2) na região tumoral. Em 28 dias houve remissão completa com áreas macroscópicas sugestivas de tecido cicatricial. O tempo livre de doença foi de 365 dias sem terapia adjuvante. Entretanto, aos 435 dias do procedimento (D0), houve recidiva na região dos incisivos com alteração respiratória. No estadiamento, foi observada metástase pulmonar sendo optado pela eutanásia humanitária devido ao prognóstico ruim. O uso da EQT para MLTB oral neste cão mostrou boa eficácia, controle local prolongado e sem alteração funcional da região.

Extraskeletal osteosarcoma (EOSA) is a rare and aggressive mesenchymal neoplasm in dogs, primarily affecting older animals, with the spleen being the most common site of involvement. This report describes a rare case of primary EOSA originating in the omentum of a 1-year-and-5-month-old spayed female dog, highlighting the role of immunohistochemistry, specifically the positive expression of vimentin and RUNX2, in confirming the tumor’s mesenchymal and osteoblastic origin. The tumor was inoperable, and treatment consisted of medical management with toceranib phosphate and losartan, with the addition of zoledronic acid following the detection of bone metastasis. The patient exhibited temporary clinical improvement for 90 days, after which disease progression was noted, including the development of abdominal effusion (1.2 liters drained). The patient survived for 180 days following diagnosis, without adverse effects related to the treatment. Necropsy confirmed widespread metastases from fibroblastic osteosarcoma, including the skin, peritoneum, lungs, heart, liver, lymph nodes, and brain, with cerebral hemorrhage as the likely cause of sudden death. Histopathological evaluation revealed extensive areas of osteoid matrix and proliferating mesenchymal cells in a disorganized arrangement, with marked vascular invasion by neoplastic emboli, as well as multifocal hemorrhage and tumor necrosis. This case illustrates a rare presentation of EOSA in a young dog and emphasizes the importance of including neoplasia in the differential diagnosis of abdominal masses, regardless of patient age. It also highlights the diagnostic value of immunohistochemical markers, particularly RUNX2, in distinguishing EOSA from other mesenchymal or reactive proliferations.

Osteosarcoma (OSA) is the most common bone tumor in dogs. It is highly aggressive, and most patients die due to metastasis, especially to the lungs. This report showed the palliative care of an unresectable appendicular OSA in a 10-year-old neutered male Labrador Retriever dog. Amputation of the affected limb was not indicated due to obesity and bilateral hip dysplasia. For this reason, palliative care with carboplatin and zoledronic acid was proposed. The treatment was well tolerated and the owner reported improvement in the lameness and pain, resulting in a good quality of life. A survival time of 30 months (910 days) was observed. Treatment with zoledronic acid and carboplatin may be considered in cases of unresectable appendicular OSA because this treatment was safe and well tolerated.

Surgery is the most used modality in the control of neoplasia. In many cases, due to the size and location of the neoplasia, the use of reconstructive techniques is necessary. Based on this, the objective of this study was to establish the prevalence of the main complications of reconstructive techniques after nodulectomy in dogs and cats. This study was a retrospective non-randomized study of three institutions. A total of 153 reconstructive procedures with postoperative complications were included in the analysis. Data was obtained from medical records. The most reported postoperative complications were ischemic necrosis and suture dehiscence. The observation period for postoperative complications corresponded to a mean time of five days (range 15 to 70 days) for ischemic necrosis, seven days for suture dehiscence, three days for seroma formation, two days for hematoma and four days for the occurrence of infection. Regarding surgical technique, there was no significant difference in the occurrence of complications in axial pattern flaps and subdermal pattern flaps. Despite surgical complications, postoperative management with careful wound care leads to healing in the vast majority of patients. These findings may help in prognosis and decision-making regarding the main reconstructive complications.

Background: Cutaneous mast cell tumor (MCT) is one of the most common skin neoplasms in cats and typically exhibits clinically benign behavior. Multiple MCTs, recurrent tumors, or infiltrated lymph nodes are associated with a more guarded prognosis. Surgery is the treatment of choice. However, the presence of multiple or large tumors can make the procedure challenging. Electrochemotherapy (ECT) is an effective local treatment, suitable for managing cutaneous or subcutaneous malignant tumors. This case series describes the first report of the use of ECT in the treatment of four cats with MCT. Case Description: Three cats presented with multiple MCTs, ranging from 7 to 50 nodules measuring 0.2 to 1 cm over the head and trunk, and one cat with a large tumor on the head measuring 4.6 cm. None of the patients had macroscopic metastasis detected on complete staging. Based on the anatomic region and limitations of systemic treatment, we proposed the use of ECT with intravenous bleomycin (15,000 IU/m²) as an alternative approach, and complete resolution of the tumors was observed in all patients after treatment. No tumor recurrence was detected during the follow-up period (range: 210–810 days). However, one patient developed new lesions at day 210. Local toxicity induced by ECT was graded as 1 (mild swelling) on a 6-point arbitrary scale (grades 0-5), and alopecia and scar tissue were observed after complete tumor remission. The number of ECT sessions ranged from one to two, with intervals of 14 to 45 days between sessions. Conclusion: The use of ECT may be successfully applied as a viable alternative approach for solitary or multiple mast cell tumors in feline patients as an alternative to surgery or in refractory cases, without significant toxicity, as observed in this case series report. Further research is warranted to support these preliminary findings.

Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors in cats that originate from interstitial cells of Cajal (ICC). ICCs are mesenchymal cells found within the muscle layers of the alimentary tract that facilitate communication between the autonomic nervous system and smooth muscles. In this case, lapatinib, a tyrosine kinase inhibitor (TKI) that targets EGFR1 and HER2, was used as part of precision therapy for metastatic GIST in an 8-year-old, 2.7 kg, spayed, female mixed-breed cat, guided by the high expression of these receptors in the tumor. The treatment resulted in partial remission of liver metastases, with a progression-free survival of 171 days and an overall survival of 192 days after starting lapatinib. Lapatinib was well tolerated, with minimal adverse gastrointestinal effects. These findings highlight the potential role of molecular profiling in guiding targeted therapy for feline GISTs and suggest that lapatinib may be a viable treatment option for EGFR1/HER2-positive tumors. Further studies are needed to evaluate the efficacy and safety of TKIs in veterinary oncology, as well as their impact on long-term survival and quality of life in feline patients with GISTs. Os tumores estromais gastrointestinais (GISTs) são tumores mesenquimais incomuns em gatos, originados a partir das células intersticiais de Cajal (ICC). As ICC são células mesenquimais encontradas dentro das camadas musculares do trato alimentar e desempenham um papel na comunicação entre o sistema nervoso autônomo e o músculo liso. Neste caso, o lapatinibe, um inibidor de tirosina quinase (ITQ), que atua sobre EGFR1 e HER-2, foi utilizado como parte de uma terapia de precisão para um GIST metastático em uma gata, sem raça definida, castrada, de 8 anos de idade, com 2,7 kg. O tratamento foi guiado pela alta expressão desses receptors no tumor. A terapia resultou em remissão parcial das metástases hepáticas, com sobrevida livre de progressão de 171 dias, e sobrevida global de 192 dias, após o início do lapatinibe. A medicação foi bem tolerada, com efeitos adversos gastrointestinais mínimos. Esses achados destacam o potencial papel do perfil molecular na orientação da terapia direcionada para GISTs felinos e sugerem que o lapatinibe pode ser uma opção viável de tratamento para tumores positivos para EGFR1/HER-2. Estudos adicionais são necessários para avaliar a eficácia e a segurança dos ITQs na oncologia veterinária, bem como seu impacto na sobrevida a longo prazo e na qualidade de vida de pacientes felinos com GISTs.

The use of tyrosine kinase inhibitors (TKI) has been growing in veterinary oncology and in the past few years several TKI have been tested in dogs. However, different from human medicine, we lack strategies to select patients to be treated with each TKI. Therefore, this study aimed to screen different tumor subtypes regarding TKI target immunoexpression as a predictor strategy to personalize the canine cancer treatment. It included 18 prostatic carcinomas, 36 soft tissue sarcomas, 20 mammary gland tumors, 6 urothelial bladder carcinomas, and 7 tumors from the endocrine system. A total of 87 patients with paraffin blocks were used to perform immunohistochemistry (IHC) of human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptors 1 (EGFR1), vascular endothelial growth factor receptor 2 (VEGFR-2), platelet derived growth factor receptor beta (PDGFR-β), c-KIT, and extracellular signal-regulated kinase 1/2 (ERK1/ERK2). The immunohistochemical screening revealed a heterogeneous protein expression among histological types with mesenchymal tumors showing the lowest expression level and carcinomas the highest expression. We have demonstrated by IHC screening that HER2, EGFR1, VEGFR-2, PDGFR-β and ERK1/ERK2 are commonly overexpressed in dogs with different carcinomas, and KIT expression is considered relatively low in the analyzed samples.

Splenic tumors are very common in dogs, and canine hemangiosarcoma (HSA) is one of the most important malignant splenic tumors. Surgery followed by chemotherapy (anthracycline-based protocols) is recommended for treating canine HSA; however, patients still do not achieve long-term survival. Therefore, this research aimed to assess vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet-derived growth factor receptor-β (PDGFR-β) gene expression in formalin-fixed tissues, evaluate the quality of mRNA for quantitative polymerase chain reaction (qPCR) analysis and identify drug repositioning candidates based on VEGFR-2 and PDGFR-β. qPCR analysis identified the relative expression of heterogeneous VEGFR-2 and PDGFR-β, with samples showing no transcripts or very low expression and those with higher relative quantification for both genes. We then used immunohistochemistry to correlate the relative quantification of VEGFR-2 and PDGFR-β transcripts with respective higher protein expression to validate our results. In the next step, we evaluated drug repositioning candidates and identified small molecule inhibitors (i.e. sorafenib) and natural compounds (curcumin and resveratrol) with the ability to block VEGFR-2 and PDGFR-β genes. Overall, our results indicated that VEGFR-2 and PDGFR-β expression is highly variable among canine HSA samples and different drugs can block the expression of both genes. Therefore, a personalized approach could be useful for selecting anti-VEGFR-2 and PDGFR-β therapies and both genes are potential candidates for future oncological panels. Os tumores esplênicos são muito comuns em cães, e o hemangiosarcoma (HSA) é um dos tumores esplênicos malignos mais importantes em cães. A cirurgia seguida de quimioterapia (protocolos baseados em antraciclinas) é a abordagem terapêutica mais recomendada para o tratamento da HSA canino; no entanto, os pacientes ainda não alcançam longa sobrevida após tratamento. Portanto, esta pesquisa teve como objetivo avaliar a expressão do receptor do fator de crescimento endotelial vascular-2 (VEGFR-2) e do receptor do fator de crescimento derivado de plaquetas-β (PDGFR-β) em tecidos fixados em formalina e identificar candidatos ao reposicionamento de medicamentos baseado na expressão desses genes. A análise qPCR identificou a expressão relativa heterogênea de VEGFR-2 e PDGFR-β, com amostras sem transcritos ou com expressão muito baixa ou amostras com alta quantificação relativa para ambos os genes. Em seguida, foi realizada o exame imuno-histoquímico para correlacionar a quantificação relativa dos transcritos de VEGFR-2 e PDGFR-β com a respectiva maior expressão proteica para validar nossos resultados. Na próxima etapa, avaliamos candidatos ao reposicionamento de medicamentos e identificamos inibidores de moléculas pequenas (ou seja, sorafenibe) e compostos naturais (curcumina e resveratrol) com capacidade de bloquear os genes VEGFR-2 e PDGFR-β. No geral, nossos resultados indicaram que a expressão de VEGFR-2 e PDGFR-β é altamente variável entre amostras caninas de HSA e diferentes drogas podem bloquear a expressão de ambos os genes. Portanto, uma abordagem personalizada poderia ser útil para selecionar terapias anti-VEGFR-2 e PDGFR-β e ambos os genes são potenciais candidatos para futuros painéis oncológicos.

Background: Primary ureteral neoplasms are extremely rare in dogs, and ureteral involvement usually occurs owing to the invasion of renal and bladder tumors. Case Description: This case report describes a 12-year-old intact male mixed-breed dog referred to a private clinic with a six-month history of abdominal distention. A physical examination revealed mild abdominal pain. Hematological tests detected normocytic-normochromic anemia (hematocrit 33.6% [reference interval-RI: 37-55%], red blood cells 4.93 M/µL [RI: 5.5-8.5 M/µL] and hemoglobin 12.4 g/dL [RI: 12-18.0 g/dL]). The results from the leukogram, thrombogram, renal, and hepatic panels were within the reference intervals for dogs. Abdominal ultrasonography revealed a cavitary mass measuring approximately 12 cm in diameter as the largest tumor in the left abdominal region over the left hepatic lobe or mesenteric site. Chest radiography did not reveal any metastasis. Therefore, the patient underwent exploratory laparotomy, during which the left ureter was found to be affected by a 12-centimeter mass that adhered to the left kidney. A unilateral left ureteronephrectomy was performed, and histology and immunohistochemistry confirmed well-differentiated primary ureteral leiomyosarcoma. The patient survived for 130 days but died of lung metastasis. Conclusion: Ureteral leiomyosarcoma should be investigated and included in the list of differential diagnoses for primary ureteral neoplasms. Regardless of the therapeutic modality, the prognosis of ureteral leiomyosarcoma may be unfavorable, as shown in this report.