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-medullary extra-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 spinal cord 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 biological behaviour, incidence and prognostic are rarely documented. Chemotherapy with melphalan and prednisolone represent the most used protocol for multiple myeloma. However, in SOP, the combination of chemotherapy with local approaches is controversial before the evidence of systemic disease. This paper aims at reporting a case of SOP in a lumbar vertebrae of 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, through cytology. The dog´s poor clinical condition and aggressive temper, associated with suspicious of an advanced myeloma-related disorder, resulted in the decision for humanized euthanasia. At necropsy, a pale, friable and hemorrhagic mass was 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 power fields, compatible with extramedullary plasmacytoma of the mature type, in the lumbar vertebrae (SOP). It was also seen myeloma-related lesions in the skin and subcutaneous, prostate, heart, superficial mandibular and axillary lymph nodesDiscussion: Solitary osseous plasmacytoma is a myeloma-related disorder rarely reported in dogs. Its biological behaviour is poorly characterized, however progression for multiple myeloma is common in humans and dogs, and it is related to a poor outcome. As the present report, systemic progression of SOP has been previously described and although an overt bone marrow infiltration was not detected, such possibility can not be excluded, once multiple myeloma distribution in the bone marrow is often multifocal. Although chemotherapy is the treatment of choice for multiple myeloma, its indication for SOP is conditioned to the evidence of systemic disease. It might delay tumour progression, but its early implementation may favor the selection of resistant neoplastic clones, making it ineffective when progression to multiple myeloma occurs. In humans radiotherapy is the treatment of choice for SOP, however it may be indicated in association to surgery. A retrospective study showed a higher survival rate in patients with SOP in the axial skeleton, which received surgical treatment combined with radiotherapy, if compared to those treated with surgery or radiotherapy alone. Decision for euthanasia was made based on the suspicious of advanced myeloma-related disorder, patient´s medical condition and aggressive temper, which limited diagnostic investigation and treatment

English (USA)

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 maypartially 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.Keywords: dog, mast cell, chemotherapy, masitinib, toceranib

English (USA)

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 maypartially 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.Keywords: dog, mast cell, chemotherapy, masitinib, toceranib

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-medullary extra-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 spinal cord 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 biological behaviour, incidence and prognostic are rarely documented. Chemotherapy with melphalan and prednisolone represent the most used protocol for multiple myeloma. However, in SOP, the combination of chemotherapy with local approaches is controversial before the evidence of systemic disease. This paper aims at reporting a case of SOP in a lumbar vertebrae of 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, through cytology. The dog´s poor clinical condition and aggressive temper, associated with suspicious of an advanced myeloma-related disorder, resulted in the decision for humanized euthanasia. At necropsy, a pale, friable and hemorrhagic mass was 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 power fields, compatible with extramedullary plasmacytoma of the mature type, in the lumbar vertebrae (SOP). It was also seen myeloma-related lesions in the skin and subcutaneous, prostate, heart, superficial mandibular and axillary lymph nodesDiscussion: Solitary osseous plasmacytoma is a myeloma-related disorder rarely reported in dogs. Its biological behaviour is poorly characterized, however progression for multiple myeloma is common in humans and dogs, and it is related to a poor outcome. As the present report, systemic progression of SOP has been previously described and although an overt bone marrow infiltration was not detected, such possibility can not be excluded, once multiple myeloma distribution in the bone marrow is often multifocal. Although chemotherapy is the treatment of choice for multiple myeloma, its indication for SOP is conditioned to the evidence of systemic disease. It might delay tumour progression, but its early implementation may favor the selection of resistant neoplastic clones, making it ineffective when progression to multiple myeloma occurs. In humans radiotherapy is the treatment of choice for SOP, however it may be indicated in association to surgery. A retrospective study showed a higher survival rate in patients with SOP in the axial skeleton, which received surgical treatment combined with radiotherapy, if compared to those treated with surgery or radiotherapy alone. Decision for euthanasia was made based on the suspicious of advanced myeloma-related disorder, patient´s medical condition and aggressive temper, which limited diagnostic investigation and treatment