Canine mast cell tumour lomustine's sensitization by tyrosine kinase inhibitors

Background: Tyrosine kinase inhibitors (TKIs) may sensitize neoplasms to conventional antineoplastic agents, however such studies are scarse in the veterinary literature and there is no in vivo study about this subject. Although the literature recommend consensual about the use of masitinib for unresectable or metastatic MCTs, the potential of tumour sensitization to chemotherapeutic agents exerted by the drug is poorly explored in veterinary medicine. The objective of this paper was to report, for the first time, the sensitization of 2 canine mast cell tumours (MCTs) to lomustine, with the use of 2 tyrosine kinase inhibitors: masitinib and toceranib. Cases: Two dogs were referred due tumour recurrence in the left pelvic limb (dog 1), and unilateral mass in the right nasal mucocutaneous region (dog 2). The first case was a 8-year-old female Pinscher, and the second case refers to a 8-year-old male mixed-breed dog. Fine needle aspiration of both lesions was performed, and the cytological analysis were compatible with high grade canine MCT. In the first case, it was started a chemotherapeutic treatment with intravenous vinblastine (2 mg/m² ), associated with prednisolone (40 mg/m2 , every 24 h for 7 days), followed by 25 mg/m2 every 24 h, for more 30 days, tramadol (4 mg/kg every 8 h, until new recommendations) and gabapentin (3 mg/kg every 12 h, until new recommendations). However, there was no objective response, and vinblastine was substituted by lomustine (60 mg/m2 every 21 days), however there was also no response after 2 doses. After masitinib importation, the same was started at 12.5 mg/kg orally every 24 h, but there was also no objective response. However, after new lomustine administration the lesion showed complete remission. The second dog initiated its treatment with toceranib, recently licensed in Brazil, at a dosage of 2.7 mg/kg every 48 h, and after 30 days, there was partial remission. However, the remaining lesion still deemed unresectable, and systemic chemotherapy with lomustine (50 mg/m2 ) was initiated along with continuous toceranib. After 3 weeks of the first chemotherapy complete remission was noted and a second dose was administered. Once the patient remained in complete clinical remission, only toceranib was maintained at the same dose. After 11 months using the toceranib, there was sign of disease recurrence and lomustine was re-initiated resulting in complete remission. Discussion: The TKIs masitinib and toceranib might be considered the first-line therapy for unresectable and/or metastatic canine MCT, but also for those cases with confirmed internal tandem duplications in the exon 11 of the c-KIT protooncogene. Masitinib appears to be more selective than others TKI, such as toceranib, imatinib, dasatinib and sunitinib, because it causes weak inhibition of BCR/ABL (breakpoint cluster region-Abelson), Fms (macrophage colony-stimulating factor receptor), Flt-3 (FMS-like tyrosine kinase-3) and VEGFR (vascular endothelial growth factor receptor), which may partially explains its increased safety and lower risk of cardiotoxicity. In the first case, the animal has been treated with lomustine associated to masitinib and showed a progression-free interval of 33 days, however, the response reported may have been lower, due previously exposition to chemotherapeutic agents, which might compromise the response to TKI. The second case, with the association of lomustine and toceranib, was followed up for 365 days, presenting only one recurrence in the final third of the follow-up, however, with subsequent new complete remission. Sensitization of canine MCT to lomustine with TKIs increases the therapeutic possibilities for this neoplasm, mainly in patients with advanced stage and high-grade tumours.

Clinical, cytological, histopathological and immunohistochemical features of a T-Zone lymphoma in a mixed-breed dog

Background: Non-Hodgkin lymphoma are a group of lymphoid neoplasms originating from the proliferation of precursors or mature, T, B and/or NK lymphocytes. T-Zone lymphoma (TZL) is characterized as an indolent lymphoma due to its slow progression and poor chemotherapys response. Dogs affected by this neoplasm may live for many years without clinical signs and are often underdiagnosed. The aim of this study was to report a TZL case in a 9-year-old male mixed breed dog, submitted to clinical follow-up and chemotherapy. Case: A 9-year-old male mixed-breed dog was presented due to the observation of an increased left mandibular lymph node. The previous cytological examination was suggestive of reactive hyperplasia and histopathological examination, by incisional biopsy, compatible with lymphocytic low-grade lymphoma. Physical examination revealed enlarged and firm left mandibular lymph node and adequate physical condition. A cytological examination was performed on the mandibular and both popliteal lymph nodes and revealed many small lymphocytes with hyperchromatic chromatin, rarely evident nucleolus and whose cytoplasm often projected in the form of a “hand-mirror” or “comet tail”, compatible with lymphocytic lymphoma (low grade) and suggestive of TZL, in the three assessed lymph nodes. The histopathological and immunohistochemical examination, of the mandibular lymph node were chosen to confirm the diagnosis. In histopathology it was observed that 40% of the sample contained a monotonous cell population, composed by small lymphocytes, with some presenting “hand-mirror” morphology. Two mitotic figures were evidenced per field of high magnification (40x), inferring a low-grade disease. Immunohistochemical analysis revealed neoplastic proliferation with immunolabeling of CD3 lymphocytes and positivity for Ki-67 in 48% of neoplastic cells, but negative for CD20, CD79a, CD45, MUM-1 and...(AU)

Clinical, cytological, histopathological and immunohistochemical features of a T-Zone lymphoma in a mixed-breed dog

Background: Non-Hodgkin lymphoma are a group of lymphoid neoplasms originating from the proliferation of precursors or mature, T, B and/or NK lymphocytes. T-Zone lymphoma (TZL) is characterized as an indolent lymphoma due to its slow progression and poor chemotherapy’s response. Dogs affected by this neoplasm may live for many years without clinical signs and are often underdiagnosed. The aim of this study was to report a TZL case in a 9-year-old male mixed breed dog, submitted to clinical follow-up and chemotherapy. Case: A 9-year-old male mixed-breed dog was presented due to the observation of an increased left mandibular lymph node. The previous cytological examination was suggestive of reactive hyperplasia and histopathological examination, by incisional biopsy, compatible with lymphocytic low-grade lymphoma. Physical examination revealed enlarged and firm left mandibular lymph node and adequate physical condition. A cytological examination was performed on the mandibular and both popliteal lymph nodes and revealed many small lymphocytes with hyperchromatic chromatin, rarely evident nucleolus and whose cytoplasm often projected in the form of a “hand-mirror” or “comet tail”, compatible with lymphocytic lymphoma (low grade) and suggestive of TZL, in the three assessed lymph nodes. The histopathological and immunohistochemical examination, of the mandibular lymph node were chosen to confirm the diagnosis. In histopathology it was observed that 40% of the sample contained a monotonous cell population, composed by small lymphocytes, with some presenting “hand-mirror” morphology. Two mitotic figures were evidenced per field of high magnification (40x), inferring a low-grade disease. Immunohistochemical analysis revealed neoplastic proliferation with immunolabeling of CD3 lymphocytes and positivity for Ki-67 in 48% of neoplastic cells, but negative for CD20, CD79a, CD45, MUM-1 and...

Solitary osseous plasmacytoma of a lumbar vertebrae with systemic involvement in a dog

Background: Myeloma-related disorders are characterized by proliferation of neoplastic plasma cell or immature immunoglobulin secreting B-lymphocytes, and include multiple myeloma, M-macroglobulinemia and extra-medullary plasmacytoma(cutaneous or extra-cutaneous). Solitary osseous plasmacytoma (SOP) is considered an unique entity among extra-medullaryextra-cutaneous plasmacytoma. It is an unusual neoplasia in dogs, predominantly found in middle-aged to older animals,with a higher incidence in bones of axial skeleton. Dogs with vertebral SOP present neurological signs related to spinalcord compression, but progression to multiple myeloma is related to a poor outcome. As in humans, progression to multiple myeloma occurs in most cases, although it may take months or years from its initial presentation. SOPs biologicalbehaviour, incidence and prognostic are rarely documented. Chemotherapy with melphalan and prednisolone representthe most used protocol for multiple myeloma. However, in SOP, the combination of chemotherapy with local approachesis controversial before the evidence of systemic disease. This paper aims at reporting a case of SOP in a lumbar vertebraeof a dog, with systemic involvement.Case: A 11-year old male mixed breed dog was attended presenting muscle weakness, lethargy, anorexia, adipsia and intense pain manifestation. The dog also presented multiple skin nodules, previously diagnosed as a plasmacytoma, throughcytology. The dogs poor clinical condition and aggressive temper, associated with suspicious of an advanced myelomarelated disorder, resulted in the decision for humanized euthanasia. At necropsy, a pale, friable and hemorrhagic masswas identified on the L3 lumbar vertebrae, associated with an osteolytic bone lesion and spinal cord compression. Histopathological analyses revealed proliferation of plasma cells, with pale perinuclear halo, moderate cellular pleomorphism,10 binucleated cells and 10 mitotic figures per 10 high...(AU)

Epidemiology of canine mammary gland tumours in Espírito Santo, Brazil

Background: Mammary tumours represent about 50 to 70% of all neoplasms in female dogs and their occurrence is directlyrelated to the reproductive status and patient´s age. The purpose of this research was to apply the Brazilian consensus ondiagnosis, prognosis and treatment of canine mammary tumours and to define the regional epidemiological aspects ofcanine mammary gland tumours in Vitoria metropolitan region (ES, Brazil) between 2012 and 2016 and to correlate themacroscopic characteristics such as lesion size and location of the neoplasm with histopathological diagnosis, tumoursgrade and lymph node metastasis.Materials, Methods & Results: Data were collected from the archives of the Laboratory of Animal Pathology of UVV andmedical records of patients attended at the Veterinary Hospital Prof. Ricardo Alexandre Hippler in 5 years (2012 to 2016). Theanimals were separated into groups by age to facilitate classification in the group with the highest occurrence of neoplasms. Theevaluation of the macroscopic characteristics was performed through the histopathological record described in the pathologylaboratory, for each patient, at the time of the initial evaluation. After descriptive analysis, data was correlated using Spearmanntest, and frequency dispersion was evaluated using chi-square test, both in the software Graph Pad Prism v. 6.01. This studyincluded 255 bitches and diagnosis of 486 lesions, once 48.6% of the dogs had more than one lesion, classified according tothe Brazilian Consensus for Canine Mammary Tumours and graded according to Elston and Ellis system. 86.8% of lesionswere consistent with actual mammary neoplasms, of which 67% were malignant and 20% were benign. Non-neoplastic lesionscorresponded to 7.2% of cases and 5.8% were extra-mammary neoplasms, with an increased incidence of lipomas (39.3%) andmast cell tumours (32.1%). Cross-breed dogs represented 26.7% of cases. Poodles (25.5%), Pinschers (9.8%) and Dachshund(4.7%)...(AU)

Epidemiology of canine mammary gland tumours in Espírito Santo, Brazil

Background: Mammary tumours represent about 50 to 70% of all neoplasms in female dogs and their occurrence is directlyrelated to the reproductive status and patient´s age. The purpose of this research was to apply the Brazilian consensus ondiagnosis, prognosis and treatment of canine mammary tumours and to define the regional epidemiological aspects ofcanine mammary gland tumours in Vitoria metropolitan region (ES, Brazil) between 2012 and 2016 and to correlate themacroscopic characteristics such as lesion size and location of the neoplasm with histopathological diagnosis, tumoursgrade and lymph node metastasis.Materials, Methods & Results: Data were collected from the archives of the Laboratory of Animal Pathology of UVV andmedical records of patients attended at the Veterinary Hospital Prof. Ricardo Alexandre Hippler in 5 years (2012 to 2016). Theanimals were separated into groups by age to facilitate classification in the group with the highest occurrence of neoplasms. Theevaluation of the macroscopic characteristics was performed through the histopathological record described in the pathologylaboratory, for each patient, at the time of the initial evaluation. After descriptive analysis, data was correlated using Spearmanntest, and frequency dispersion was evaluated using chi-square test, both in the software Graph Pad Prism v. 6.01. This studyincluded 255 bitches and diagnosis of 486 lesions, once 48.6% of the dogs had more than one lesion, classified according tothe Brazilian Consensus for Canine Mammary Tumours and graded according to Elston and Ellis system. 86.8% of lesionswere consistent with actual mammary neoplasms, of which 67% were malignant and 20% were benign. Non-neoplastic lesionscorresponded to 7.2% of cases and 5.8% were extra-mammary neoplasms, with an increased incidence of lipomas (39.3%) andmast cell tumours (32.1%). Cross-breed dogs represented 26.7% of cases. Poodles (25.5%), Pinschers (9.8%) and Dachshund(4.7%)...

Solitary osseous plasmacytoma of a lumbar vertebrae with systemic involvement in a dog

Background: Myeloma-related disorders are characterized by proliferation of neoplastic plasma cell or immature immunoglobulin secreting B-lymphocytes, and include multiple myeloma, M-macroglobulinemia and extra-medullary plasmacytoma(cutaneous or extra-cutaneous). Solitary osseous plasmacytoma (SOP) is considered an unique entity among extra-medullaryextra-cutaneous plasmacytoma. It is an unusual neoplasia in dogs, predominantly found in middle-aged to older animals,with a higher incidence in bones of axial skeleton. Dogs with vertebral SOP present neurological signs related to spinalcord compression, but progression to multiple myeloma is related to a poor outcome. As in humans, progression to multiple myeloma occurs in most cases, although it may take months or years from its initial presentation. SOP’s biologicalbehaviour, incidence and prognostic are rarely documented. Chemotherapy with melphalan and prednisolone representthe most used protocol for multiple myeloma. However, in SOP, the combination of chemotherapy with local approachesis controversial before the evidence of systemic disease. This paper aims at reporting a case of SOP in a lumbar vertebraeof a dog, with systemic involvement.Case: A 11-year old male mixed breed dog was attended presenting muscle weakness, lethargy, anorexia, adipsia and intense pain manifestation. The dog also presented multiple skin nodules, previously diagnosed as a plasmacytoma, throughcytology. The dog’s poor clinical condition and aggressive temper, associated with suspicious of an advanced myelomarelated disorder, resulted in the decision for humanized euthanasia. At necropsy, a pale, friable and hemorrhagic masswas identified on the L3 lumbar vertebrae, associated with an osteolytic bone lesion and spinal cord compression. Histopathological analyses revealed proliferation of plasma cells, with pale perinuclear halo, moderate cellular pleomorphism,10 binucleated cells and 10 mitotic figures per 10 high...