Mutations of the c-KIT gene in canine mast cell tumors and respective nodal metastases classified according to mast cell infiltration / Mutações no gene c-KIT em mastocitomas caninos e respectivas metástases nodais classificados segundo a infiltração de mastócitos

The molecular background of canine mast cell tumors (MCT) has been extensively investigated; however, the dynamic molecular changes that occur during carcinogenesis and metastasis are not fully understood. This study aimed to evaluate the incidence of mutations in the c-KIT proto-oncogene in canine MCTs and relative draining regional lymph nodes. Suspected or confirmed lymph node metastasis was classified accordingly to the HN Weishaar classification. The study included 34 dogs diagnosed with MCT; 19 patients were enrolled prospectively. These dogs had the primary MCT and regional lymph node resected and analyzed simultaneously. The second group was evaluated retrospectively and included fifteen patients resectioning the primary MCT without evaluation of regional lymph node. Analyzes of c-KIT mutation were performed for all primary MCTs and, in the first group, compared between primary MCT and HN-classified metastasis. Internal tandem duplications (ITD) in exon 11 of the c-KIT gene were detected in 20% of patients. Ten of the nineteen patients (52%) in the first group presented mast cell infiltration in the regional lymph node, and ITD in exon 11 of the c-KIT gene was detected in five and two dogs from Groups 1 and 2, respectively. ITD c-KIT mutations are common in canine MCT and may be found in the draining lymph node metastases/mast cell infiltrates in the absence of mutation of the primary tumor. Evaluation of c-KIT mutation in the primary tumor and metastases may be informative for defining both prognosis and therapeutic options in MCT cases.

O perfil molecular do mastocitoma (MCT) tem sido bastante investigado, no entanto as dinâmicas moleculares que ocorrem durante a carcinogênese e metástase desta neoplasia não estão bem esclarecidas. O objetivo desse estudo foi avaliar a incidência de mutações no proto-oncogene c-KIT em MCTs caninos e respectivos linfonodos regionais. Os casos suspeitos ou confirmados de metástase para os linfonodos, foram classificados de acordo com a classificação HN de Weishaar. O estudo incluiu 34 cães diagnosticados com MCT e, desses, 19 pacientes foram avaliados de maneira prospectiva, em que o tumor primário e o linfonodo regional foram ressecados e analisados simultaneamente. O segundo grupo foi avaliado retrospectivamente e incluiu quinze pacientes que tiveram ressecção do MCT primário sem avaliação de linfonodo regional. A análise da mutação c-KIT foi realizada para todos os MCTs primários e, no primeiro grupo, comparados entre MCT primário e metástase classificada pelo sistema HN. Duplicações internas em tandem (DIT), no exon 11 do gene c-KIT, foram detectadas em um total de 20% dos pacientes. Dez dos dezenove pacientes (52%) do primeiro grupo apresentavam infiltração de mastócitos no linfonodo regional, e DIT no exon 11 do gene c-KIT foram identificadas em cinco e dois cães dos Grupos 1 e 2, respectivamente. Mutações do tipo DIT no gene c-KIT são comuns no MCT canino e podem estar presentes nas metástases/infiltrados de mastócitos na ausência de mutação do tumor primário. A avaliação da mutação no gene c-KIT no tumor primário e metástases pode ser informativa para definir tanto o prognóstico quanto as opções terapêuticas em casos de MCT.

Clinical, histopathological and immunohistochemical features ofa thymoma in a domestic rabbit (Oryctolagus cuniculus): casereport

Thymoma is a neoplasm originating from epithelial cells of the thymus. It represents the most common tumor in the mediastinal region of rabbits, followed by lymphoma. This study aims to report a case of post mortem diagnosis of thymoma in a rabbit (Oryctolagus cuniculus), with the purpose to contribute to the understanding of this disease and its diagnosis in this specie. A six-year-old male mixed breed pet rabbit (O. cuniculus), weighing 2.3 kg, was referred to necropsy exam. The previous clinical history included prostration, lethargy, weight loss, dysorexia and respiratory distress, evidenced mainly on the expiratory phase. Radiographs revealed pleural effusion and the presence of a mass involving the cranial and middle mediastinum, confirmed by ultrasound. In the cytological examination, it was diagnosed as a low-gradelymphoma and chemotherapy was performed with COP (cyclophosphamide, vincristine Oncovin®, prednisolone). However, after 145 days, euthanasia was performed. At necropsy, a well delimited mass was observed in the mediastinal region, adhered to the pleura, with firm consistency and pale coloration. Histopathological analysis of the mass showed the proliferation of epithelial neoplastics cells, arranged in trabeculas and with infiltration of small lymphocytes. The immunohistochemical findings included cytoplasmic immunolabeling for cytokeratin AE1/AE3 in 90% of epithelial neoplastics cells, while CD3 was evidenced in a small number of lymphocytes (T-lymphocytes) and CD79a in Blymphocytes localized on the neoplasia periphery. The growth fraction was estimated at 30% by Ki-67. According to the histopathological criteria for thymoma classification proposed by the World Health Organization, 2015, it was made the diagnosis of lymphocyte-rich predominantly cortical thymoma (B1 type).(AU)

Clinical, histopathological and immunohistochemical features ofa thymoma in a domestic rabbit (Oryctolagus cuniculus): casereport

Thymoma is a neoplasm originating from epithelial cells of the thymus. It represents the most common tumor in the mediastinal region of rabbits, followed by lymphoma. This study aims to report a case of post mortem diagnosis of thymoma in a rabbit (Oryctolagus cuniculus), with the purpose to contribute to the understanding of this disease and its diagnosis in this specie. A six-year-old male mixed breed pet rabbit (O. cuniculus), weighing 2.3 kg, was referred to necropsy exam. The previous clinical history included prostration, lethargy, weight loss, dysorexia and respiratory distress, evidenced mainly on the expiratory phase. Radiographs revealed pleural effusion and the presence of a mass involving the cranial and middle mediastinum, confirmed by ultrasound. In the cytological examination, it was diagnosed as a low-gradelymphoma and chemotherapy was performed with COP (cyclophosphamide, vincristine – Oncovin®, prednisolone). However, after 145 days, euthanasia was performed. At necropsy, a well delimited mass was observed in the mediastinal region, adhered to the pleura, with firm consistency and pale coloration. Histopathological analysis of the mass showed the proliferation of epithelial neoplastics cells, arranged in trabeculas and with infiltration of small lymphocytes. The immunohistochemical findings included cytoplasmic immunolabeling for cytokeratin AE1/AE3 in 90% of epithelial neoplastics cells, while CD3 was evidenced in a small number of lymphocytes (T-lymphocytes) and CD79a in Blymphocytes localized on the neoplasia periphery. The growth fraction was estimated at 30% by Ki-67. According to the histopathological criteria for thymoma classification proposed by the World Health Organization, 2015, it was made the diagnosis of lymphocyte-rich predominantly cortical thymoma (B1 type).

Simultaneous osteosarcoma in two limbs of a Maltese dog

Osteosarcoma (OSA) is rarely diagnosed in small breed dogs and it is usually restricted to a single bone, despite its aggressive biological behavior. This paper aims to report a rare case of OSA in an eight-year-old female spayed Maltese dog with simultaneous presentation in thoracic and pelvic limbs, associated with lung and kidney micrometastasis. Physical exam revealed an increase volume in the distal region of the left femur and in the proximal region of the left humerus with intense pain sensibility at palpation. Pelvic limb´s radiographs revealed an extensive area of bone lysis in the distal femur, lamellated periosteal reaction and formation of the Codman triangle, while in the thoracic limb, it was evident a cortical fracture of the proximal humerus and mixed periosteal reaction, suggestive of neoplastic or infectious disease. Cytological analysis showed the presence of a large number of malignant star-shaped cells, with prominent anisocytosis and anisokaryosis, moderate to prominent cellular and nuclear pleomorphism, rare mitotic figures, besides abundant extracellular matrix compatible with osteoid, suggestive of osteosarcoma. Histopathological findings were compatible with OSA. The dog died of a cardiorespiratory arrest and necropsy revealed a grade II osteoblastic osteosarcoma in the humerus and femur, along with renal metastasis and neoplastic emboli in the kidney and lungs.

Simultaneous osteosarcoma in two limbs of a Maltese dog

Osteosarcoma (OSA) is rarely diagnosed in small breed dogs and it is usually restricted to a single bone, despite its aggressive biological behavior. This paper aims to report a rare case of OSA in an eight-year-old female spayed Maltese dog with simultaneous presentation in thoracic and pelvic limbs, associated with lung and kidney micrometastasis. Physical exam revealed an increase volume in the distal region of the left femur and in the proximal region of the left humerus with intense pain sensibility at palpation. Pelvic limb´s radiographs revealed an extensive area of bone lysis in the distal femur, lamellated periosteal reaction and formation of the Codman triangle, while in the thoracic limb, it was evident a cortical fracture of the proximal humerus and mixed periosteal reaction, suggestive of neoplastic or infectious disease. Cytological analysis showed the presence of a large number of malignant star-shaped cells, with prominent anisocytosis and anisokaryosis, moderate to prominent cellular and nuclear pleomorphism, rare mitotic figures, besides abundant extracellular matrix compatible with osteoid, suggestive of osteosarcoma. Histopathological findings were compatible with OSA. The dog died of a cardiorespiratory arrest and necropsy revealed a grade II osteoblastic osteosarcoma in the humerus and femur, along with renal metastasis and neoplastic emboli in the kidney and lungs.(AU)