Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study

BACKGROUND: Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). MATERIAL AND METHODS: Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. RESULTS: 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3\u2009cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. CONCLUSION: Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3\u2009cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT

Ultrasonographic honeycomb pattern of the spleen in cats: correlation with pathological diagnosis in 33 cases

Objectives: The aim of this study was to evaluate the relationship between the ultra sonographic (US) diffuse honeycomb pattern (HCP) of the spleen and a pathological diagnosis in cats, and to assess the influence of transducer type on HCP visualisation. Methods: Abdominal ultrasounds of cats with an HCP were reviewed and splenic size, shape, margination, other parenchymal alterations and splenic hilar lymphadenopathy were recorded. When applicable, images acquired with high-frequency linear and curvilinear transducers were compared to determine if an HCP was more frequently demonstrated on high-resolution images. A retrospective review of the corresponding splenic cyto histopathological samples was also performed. Results: Thirty-three cats met the inclusion criteria. Five cases were diagnosed by histology and 28 by cytology, confirmed by PCR for antigen receptor rearrangements (PARR) in uncertain cases. There were 15 cases of lymphoid hyperplasia, eight cases of lymphoma (four B cell, three T cell and one large granular lymphocytes), six cats with splenitis, three with extramedullary haematopoiesis and one with histiocytic sarcoma. The prevalence of lymphoma in cats with an HCP of the spleen was 24%. Splenomegaly was the most frequent US feature associated with an HCP and was observed in all lymphoma cases. In the images obtained from both high-frequency linear and micro-convex transducers the visualisation of an HCP was enabled in all cases (24/24) and in 62.5% (15/24), respectively. Conclusions and relevance: Based on our findings, an US HCP of the spleen in cats can be associated with benign and malignant disorders and is infrequently associated with lymphoma in comparison with dogs. Cytological or histological examination, possibly supplemented by PARR, should always be performed for diagnostic support. Use of high-frequency linear transducers is recommended to properly recognise an HCP or subtle changes in splenic parenchyma

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era. Selecting cases, matching clinical benefit. A position paper from the Italian Group of Haematopathology (G.I.E.)

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient

Periarticular histiocytic sarcoma with heart metastasis in a cat

A 4-year-old intact female domestic short-haired cat was referred for recommendations about adjuvant medical treatment 1&nbsp;month after left forelimb amputation due to periarticular histiocytic sarcoma (HS). At presentation, physical abnormalities were limited to enlarged ipsilateral superficial cervical and axillary lymph nodes. Routine blood analysis, abdominal ultrasound, and thoracic radiology were unremarkable. The cat initially received lomustine without any adverse events. Four weeks later, the cat developed severe acute respiratory distress. Results of thoracic radiographs and transthoracic echocardiographic analysis were suggestive of pulmonary and heart metastasis. Due to the cat's poor clinical condition and prognosis, the owner elected euthanasia, and a necropsy was performed. Based on gross pathology, histopathology, and immunohistochemistry, an HS with nodal, renal, pulmonary, and heart (right auricular and right ventricular) metastases was diagnosed. This case represents the first description of HS with a heart metastasis in a cat, providing further insight into the clinical course and metastatic behavior of this rare malignant neoplasm. Clinicians should be aware of this site of metastasis and consider HS in the list of differential diagnoses for secondary heart tumors in cats

Multi-Robot Adversarial Resilience using Control Barrier Functions

In this paper we present a control barrier functionbased (CBF) resilience controller that provides resilience in a multi-robot network to adversaries. Previous approaches provide resilience by virtue of specific linear combinations of multiple control constraints. These combinations can be difficult to find and are sensitive to the addition of new constraints. Unlike previous approaches, the proposed CBF provides network resilience and is easily amenable to multiple other control constraints, such as collision and obstacle avoidance. The inclusion of such constraints is essential in order to implement a resilience controller on realistic robot platforms. We demonstrate the viability of the CBF-based resilience controller on real robotic systems through case studies on a multi-robot flocking problem in cluttered environments with the presence of adversarial robots

Lymphadenectomy improves outcome in dogs with resected Kiupel high-grade cutaneous mast cell tumours and overtly metastatic regional lymph nodes

Historically, the prognosis for dogs with stage II Kiupel high-grade cutaneous mast cell tumours has been considered poor

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P&lt;0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Outcome comparison between radiation therapy and surgery as primary treatment for dogs with periarticular histiocytic sarcoma: An Italian Society of Veterinary Oncology study

Localized histiocytic sarcoma may occur as a primary lesion in periarticular tissues of large appendicular joints. Treatment options for the primary lesion include radical surgical excision, radiation therapy (RT), or both, in combination with chemotherapy for potential systemic metastases. In an effort to better characterize the time to progression (TTP) following surgical vs non-surgical approaches for periarticular histiocytic sarcoma (PAHS), a contemporary European population of affected dogs was retrospectively surveyed. Medical records were queried for newly-diagnosed PAHS cases undergoing surgery (predominantly limb amputation) or RT followed by systemic chemotherapy. Of 49 dogs, 34 underwent RT and 15 underwent surgery. All dogs received adjuvant chemotherapy. There was no statistically significant difference in TTP or overall survival between groups. The median TTP was 336 days for the operated dogs and 217 days for the irradiated dogs (P =.117). The median overall survival time was 398 days for the operated dogs and 240 days for the irradiated dogs (P =.142). On multi-variable analysis, the variables significantly associated with an increased risk of both tumour progression and tumour-related death were regional lymph node and distant metastasis at admission. Survival and local control rates following RT may be comparable to radical resection. These data may better inform shared decision-making processes between multi-disciplinary care providers and owners

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era: selecting cases, matching clinical benefit : A position paper from the Italian Group of Haematopathology (G.I.E.).

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient. © 2019, The Author(s)

An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species

BACKGROUND: Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit &gt; 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species. METHODS: Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were collected as normal controls. Bisulfite next generation sequencing evaluated the DNA methylation level from seven UCNEs (uc.160, uc.283, uc.416, uc.339, uc.270, uc.299, and uc.328). RESULTS: 57/59 CpGs were significantly different according to the Kruskal-Wallis test (p &lt; 0.05) comparing normal samples with SCC. A common DNA hypermethylation pattern was observed in SCCs from all the species evaluated in this study, with an increasing trend of hypermethylation starting from normal mucosa, through stomatitis to SCC. CONCLUSIONS: Our findings indicate that UCNEs are hypermethylated in human SCC, and this behavior is also conserved among different species of mammals