Characterization of the fecal virome in dogs with chronic enteropathy.

The fecal virome has been investigated in humans and various animal species using next generation sequencing. However, limited information is available about the fecal virome of dogs with chronic enteropathy (CE). We aimed to characterize the canine fecal virome of dogs with CE and compare it with the virome of previously analyzed healthy dogs.A total of 16 adult dogs; 8 healthy dogs (data from a parallel study) and 8 dogs with CE had fecal samples assessed by viral shotgun sequencing. Fecal samples were subjected to enrichment of viral nucleic acids prior to sequencing and metagenomic analyses. Characterization of the complete genome of a canine kobuvirus was performed by Sanger sequencing. An additional 21 healthy dogs and 14 dogs with CE were further analyzed for the prevalence of canine kobuvirus.Three fecal samples from dogs with CE contained in total 3 eukaryotic viral families. In contrast, 4/8 fecal samples previously identified from healthy dogs, contained 5 eukaryotic viral families with 2 families exclusive to this group. Bacteriophages were identified in all fecal samples from CE and healthy dogs. Canine kobuvirus was identified in one dog with CE, by shotgun sequencing, and the complete genome was then characterized. This kobuvirus was classified within canine kobuvirus group, being similar to strains from Korea and China. The larger prevalence study did not detect additional samples positive for canine kobuvirus. The fecal virome of dogs with CE differs in number and type of viral families from healthy dogs. The first Australian canine kobuvirus sequence was identified and characterized from a dog with CE.

Clinicopathological analysis of 12 patients with Epstein-Barr virus-positive primary intestinal T/natural killer-cell lymphoma (EBV+ ITNKL).

AIMS: Epstein-Barr virus-positive (EBV+ ) intestinal T/natural killer (NK) cell lymphoma (ITNKL) is an uncommon tumour with an extremely aggressive clinical behaviour. However, the clinicopathological characteristics of this tumour, including T cell receptor (TCR) phenotype and the patient's background, remain unknown. The aim of this study was to elucidate the detailed clinicopathological profile of EBV+ ITNKL. METHODS AND RESULTS: We enrolled 12 patients with EBV+ ITNKL without nasal involvement into the study. All patients were characterized by involvement of the small intestine with concurrent lesions of the large intestine in two patients. Seven patients (58%) had Lugano stages IIE/IV disease and eight (67%) were categorized as high-intermediate/high-risk according to the Prognostic Index for PTCL (PIT). Three patients (25%) with an age of onset of less than 50 years had chronic active EBV infection (CAEBV). Five CD56-positive patients (42%) had a poorer prognosis than those without CD56 expression (P = 0.008). NK cell-type lymphoma defined by the absence of any TCR expression or clonal TCR-γ rearrangement was found in six patients (50%). Interestingly, EBV+ intra-epithelial lymphocytosis was observed in one case with a background of CAEBV. CONCLUSIONS: This study is the first to shed light on the significant heterogeneity of EBV+ ITNKL and its relationship with CAEBV, especially in patients younger than 50 years of age. These observations will provide a guide for diagnostic and therapeutic approaches in routine practice.

Cytotoxic T-cell and NK-cell lymphomas: current questions and controversies.

The cytotoxic T-cell and natural killer (NK)-cell lymphomas and related disorders are important but relatively rare lymphoid neoplasms that frequently are a challenge for practicing pathologists. This selective review, based on a meeting of the International Lymphoma Study Group, briefly reviews T-cell and NK-cell development and addresses questions related to the importance of precise cell lineage (αß-type T cell, γδ T cell, or NK cell), the implications of Epstein-Barr virus infection, the significance of anatomic location including nodal disease, and the question of further categorization of enteropathy-associated T-cell lymphomas. Finally, developments subsequent to the 2008 World Health Organization Classification, including the recognition of indolent NK-cell and T-cell disorders of the gastrointestinal tract are presented.

Primary intestinal T-cell and NK-cell lymphomas: a clinicopathological and molecular study from China focused on type II enteropathy-associated T-cell lymphoma and primary intestinal NK-cell lymphoma.

In China, which is a non-endemic area for celiac disease, primary intestinal T-cell and NK-cell lymphomas might comprise heterogeneous subtypes. Both type II enteropathy-associated T-cell lymphoma and primary intestinal NK-cell lymphoma are rarely reported and poorly characterized in China. In this study, we examined the clinicopathological and molecular features of 38 cases of primary intestinal T-cell and NK-cell lymphoma in Chinese patients. Based on these findings, we first classified the patients into an NK-cell group (n=6) and a T-cell group (n=32). In the NK-cell group, the mean age was 37 years. All tumors of the NK-cell group were positive for Epstein-Barr virus encoded mRNA in the majority of tumor cells and were polyclonal according to the results of commercial BIOMED-2 T-cell receptor gene rearrangement assays. The survival in the NK-cell group was significantly worse than that of the T-cell group (P=0.0247). Next, 7 tumors of the T-cell group were considered type II enteropathy-associated T-cell lymphoma, while 24 were considered peripheral T-cell lymphoma, not otherwise specified (NOS). In the type II enteropathy-associated T-cell lymphoma group, the mean age was 55 years. Type II enteropathy-associated T-cell lymphoma tumor cells from all seven patients were monomorphic, medium sized. The survival in the type II enteropathy-associated T-cell lymphoma group was significantly worse than that of the peripheral T-cell lymphoma, NOS group (P=0.0181). Multivariate analysis identified NK-cell phenotype, male gender, and CD8 positivity as factors for poor prognosis in our series of primary intestinal T-cell and NK-cell lymphoma patients. In conclusion, most cases of primary intestinal T-cell and NK-cell lymphoma in China are not associated with celiac disease and could be classified to NK-cell group, type II enteropathy-associated T-cell lymphoma group, and peripheral T-cell lymphoma, NOS group. Each group has distinctive histopathological features with prognostic significance.