Mastocytosis in the skin in dogs: A multicentric case series.

Canine cutaneous mastocytosis (CM) is rare in contrast to canine mast cell tumours. In humans, CM commonly affects children and is usually indolent with possible spontaneous resolution. Systemic mastocytosis (SM) with bone marrow involvement typically affects adults, can have a poor outcome, and often includes skin lesions. 'Mastocytosis in the skin' (MIS) is the preferred term of skin lesions, if bone marrow evaluations are not available, which is often the cases in dogs. In human SM and CM, KIT mutations are often detected. The veterinary literature suggests clinical resemblances between human and canine MIS, but data is limited, and KIT mutations are rarely assessed. This retrospective study describes clinicopathological findings, treatment and outcome of 11 dogs with suspected MIS. Dogs with multiple mast cell tumours were excluded. Histopathology reports (n = 5) or slides (n = 6) were reviewed. KIT mutation analysis including exons 8, 9, 11, 14 and 17 were analysed in eight dogs. Median age at diagnosis was 4 years (range, 1-12). Typical clinical signs included multifocal to generalised nodules and papules. Histologically, skin lesions were characterised by dermal infiltration of well-differentiated mast cells. KIT mutations were detected in 3/8 dogs (exon 9: n = 2; exon 11: n = 1). One dog had mastocytaemia suggesting possible SM. Glucocorticoids were mostly successful with lesion improvement in all treated dogs (n = 8). This cohort highlights resemblances between human and canine MIS. Further studies are required to confirm these findings and establish diagnostic criteria for CM and MIS associated with SM in dogs.

The Prognostic Role of Preoperative Hematological and Inflammatory Indices in Canine Appendicular Osteosarcoma.

Hematological indices play a prognostic role in human osteosarcoma (OSA), but data are limited in dogs. The aim of this retrospective multicentric cohort study was to investigate the prognostic significance of pre-operative hematological/inflammatory indices in a cohort of client-owned dogs with appendicular OSA receiving standardized treatment. Cut-offs associated with progression-free survival (PFS) for pre-operative hematological values/ratios were established using the minimal p-value approach. Historical prognostic factors were also assessed. Statistical analyses were performed for the whole population and after the exclusion of sighthounds. Fifty-nine dogs were included (13 were sighthounds). Multivariable analysis revealed that a low neutrophil count (<4.37 × 109/L, HR0.28, CI 95% 0.13-0.61, p = 0.001), a high red blood cell count (≥7.91, HR3.5, CI 95% 1.56-7.9, p = 0.002), and a proximal humerus location (HR3.0, CI 95% 1.48-6.1, p = 0.002) were associated with shorter PFS. In the sighthound-only population, only OSA location was significantly associated with PFS in univariable analysis. When sighthounds were excluded, a low neutrophil count, a low monocyte count, and a proximal humerus location were associated with shorter PFS, in multivariable analysis. Neutrophil count and possibly monocyte and red blood cell counts can be useful prognostic markers in canine OSA treated with amputation and adjuvant carboplatin. However, not all indices are appropriate in sighthounds.

Pre-operative neoadjuvant vinblastine-prednisolone in canine mast cell tumours: A single-centre retrospective cohort study.

Neoadjuvant chemotherapy can be used in canine mast cell tumours (MCTs) to optimise surgical margins or to enable marginal excision in challenging locations. The objective of this study was to describe the outcome of dogs with cutaneous and subcutaneous MCTs treated with neoadjuvant vinblastine-prednisolone (NA-VP). Records of treatment-naïve dogs with cutaneous/subcutaneous MCT that received NA-VP were reviewed including signalment, indication for NA-VP, staging results, clinical response, surgical data and histopathology reports. For dogs with post-operative follow-up ≥365 days, predictive factors for local recurrence (LR) were evaluated. Forty-four dogs were included. NA-VP was indicated to optimise surgical margins (group MARG) in 19 dogs (43.2%) and to enable surgery (group MORB) in 25 dogs (56.8%). Complete and partial response were documented in 40.9% of dogs and 30 dogs (68.2%) underwent surgery. The indication for NA-VP was significantly associated with undergoing surgery (p < .001) on multivariable analysis. Twelve (48%) and 18 dogs (94.7%) underwent surgery in the group MORB and MARG, respectively. Five dogs (16.7%) experienced wound dehiscence. Complete excision was achieved in 14 dogs (46.7%). In dogs undergoing surgery with ≥365 days of follow-up, LR was documented in five cases (20.8%). None of the factors analysed including mitotic count, completeness of excision and response to NA-VP were associated with LR; notably, LR occurred in 3/11 (27.2%) completely excised MCTs. In a pre-operative setting, NA-VP appears safe and could be beneficial in selected cases. Prognostic factors such as clinical response, mitotic count and completeness of excision should be interpreted with caution following NA-VP.

Canine anal sac gland carcinoma with regional lymph node metastases treated with sacculectomy and lymphadenectomy: Outcome and possible prognostic factors.

The staging system commonly used in canine anal sac gland carcinoma (ASGC) is a revised Tumour-Node-Metastasis (TNM) system published in 2007. This staging system consists in four stages and, for dogs with nodal metastases, the size of the metastatic lymph node (mLN) defines the N stage. However, we hypothesise that (1) the mLN size has no prognostic significance when the mLN can be excised, (2) a high number of mLNs is associated with poorer prognosis and (3) the measurement of the mLN on imaging is not reproducible. To investigate these hypotheses, medical records and diagnostic images of dogs with ASGC and mLN, treated with sacculectomy and lymphadenectomy, with or without chemotherapy, were reviewed. Interobserver variability for mLN measurement was assessed. Prognostic factors including mLN size and number were investigated. Time to documented progression (TDP) and disease-specific survival (DSS) were evaluated. Progression-free interval (PFI) was analysed with interval-censored data analysis. Fifty-seven dogs were included. The median PFI, TDP and DSS were 110 (95%CI 61.5-185.5), 196 (95%CI 162-283) and 340 days (95%CI 321-471), respectively. For measurement of the largest mLN, interobserver agreement was excellent but limits of agreement reached 39.7%. Neither the size of the largest mLN nor the use of adjuvant chemotherapy were associated with outcome. The number of mLNs was associated with outcome and having more than four mLNs was associated with shorter PFI (p < .001), TDP (p = .004) and DSS (p < .001). While mLN size measurement was not consistently reproducible and did not influence outcome in our cohort, number of mLNs did. Further studies are required for development of a revised staging system.

Evaluation of a multi-agent chemotherapy protocol combining dexamethasone, melphalan, actinomycin D, and cytarabine for the treatment of resistant canine non-Hodgkin high-grade lymphomas: a single centre's experience.

The DMAC protocol (dexamethasone, melphalan, actinomycin-D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non-Hodgkin high-grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first-line treatment. Thirty-five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non-responders: 62 days (range 28-952) for CR vs 32 days (range 20-70) for PR. Six CR received more than six cycles of DMAC (range 7-36 cycles) and experienced a longer TTD (median 508, range 126-952 days). Thrombocytopenia occurred in 45% (24 grade 1-2, 21 grade 3-4) and neutropenia in 36% of cases (29 grade 1-2, 7 grade 3-4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1-2, 2 grade 3-4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.