Primary pulmonary histiocytic sarcoma (PHS) has been reported, but is not well characterized. The aim of this retrospective study was to describe clinical characteristics, characterize prognostic factors and report the outcome of a larger group of dogs with primary PHS. Medical records of dogs diagnosed with primary PHS at 11 institutions were retrospectively reviewed. Thirty‐seven dogs were included; 13 received CCNU‐based chemotherapy alone, 18 received surgery and adjuvant CCNU‐based chemotherapy, 3 received medical management alone and 3 dogs received surgery alone. The overall median progression free survival (PFS) and the median survival (overall survival [OS]) were 197 and 237 days, respectively. Measurable responses were noted in dogs receiving only chemotherapy; however, responses were not durable with PFS (91 days) and OS times (131 days) shorter than overall medians. Dogs that received surgery and chemotherapy had significantly prolonged PFS (276 days, P = 0.001) and OS (374 days, P = 0.001), compared with dogs not receiving surgery. As only three dogs undergoing surgery did not receive chemotherapy, it is not possible to determine the contribution of chemotherapy as an adjuvant to surgery. Dogs without evidence of intra‐thoracic metastatic disease were much more likely to undergo surgery (odds ratio = 7.04; P = 0.018). While the presence of metastasis or clinical signs at diagnosis negatively impacted PFS, only the former negatively impacted OS. These data imply that dogs presenting with PHS amenable to surgery (ie, no clinical evidence of metastasis) benefit from surgical intervention; however, the lack of a comparable surgery alone group precludes assessment of the efficacy of post‐surgical adjuvant chemotherapy.

Canine diffuse large B-cell lymphoma (DLBCL), the most common hematologic malignancy of dogs, is associated with poor overall survival. The lack of conventional chemotherapies with sustainable efficacy warrants investigation of novel therapies. Pevonedistat (MLN4924) is a potent and selective small molecule NEDD8-activating enzyme inhibitor. In human activated B-cell-like (ABC) diffuse large B-cell lymphoma, pevonedistat induces lymphoma cell apoptosis, DNA damage and G1 cell cycle arrest by inhibiting the nuclear factor-κB (NF-κB) pathway. Genomic and transcriptomic studies showed that the NF-κB pathway is deregulated in canine DLBCL. Our results showed that pevonedistat treatment significantly reduces the viability of canine DLBCL cells by inducing G1 cell cycle arrest and apoptosis. Pevonedistat treatment inhibits NF-κB pathway activation and downregulates NF-κB target genes in canine DLBCL. Moreover, administration of pevonedistat to mice bearing canine DLBCL xenograft tumours resulted in tumour regression. Our in vivo and in vitro studies provide justification for future clinical application of pevonedistat as a potential new anti-cancer therapy that may benefit both canine and human species.