Hemophagocytic syndrome (HPS) is a rare disorder characterized by dysregulation of the immune response resulting in uncontrolled activation of macrophages with exacerbated phagocytosis of host cells. In dogs, the criteria for diagnosis include the presence of pancytopenia or bicytopenia in the peripheral blood and >2% hemophagocytic macrophages in bone marrow aspirates. When HPS is associated with lymphoma, it is called lymphoma‐associated hemophagocytic syndrome (LAHS). Here, we present a case of a 4 ½‐year‐old female spayed Old English Mastiff that presented with severe thrombocytopenia, mild anemia, mild to moderate leukopenia, and large granular lymphocytes (LGLs) in the peripheral blood. The patient had enlarged lymph nodes with many LGLs seen cytologically, leading to the interpretation of LGL lymphoma. Bone marrow displayed numerous LGLs that stained strongly for CD3 but did not show immunoreactivity to CD4 or CD8, and PCR for antigen receptor rearrangement analysis confirmed a clonal T‐cell receptor gamma gene rearrangement. The presence of ~3.5% hemophagocytes present on the bone marrow evaluation raised concern for HPS and, more specifically, LAHS. HPS and LAHS are challenging to diagnose and require many criteria to be fulfilled before a definitive diagnosis can be made; the low number of cases in the literature makes this even more challenging in dogs. This case represents secondary LAHS due to LGL lymphoma in a dog.
Urothelial carcinoma (UC) comprises up to 2% of all naturally occurring neoplasia in dogs and can be challenging to diagnose. MicroRNAs (miRNAs) have been reported to be dysregulated in numerous diseases, including neoplasia. MiRNA expression has been evaluated in human UC, but there is limited information regarding the miRNA transcriptome of UC in dogs. Our study aimed to evaluate differential miRNA expression in bladder tissue collected from normal canine urothelium and canine invasive UC (iUC) to elucidate the dysregulated pathways in canine UC. Next-Generation RNA sequencing (RNA-Seq) was performed for dogs with UC (n = 29) and normal canine urothelium (n = 4). Raw RNA data were subjected to normalization, and pairwise comparison was performed using EdgeR with Benjamini-Hochberg FDR multiple testing correction (p < 0.05; >2-fold change) comparing tissue samples of normal urothelium to canine iUC samples. Principal component analysis and hierarchical cluster analysis were performed. MiRNA of FFPE tissue samples of separate iUC (n = 5) and normal urothelium (n = 5) were used to evaluate five miRNAs using RT-qPCR. Pathway analysis was performed utilizing miRWalk, STRING database, and Metascape utilizing KEGG pathways and GO terms databases. Twenty-eight miRNAs were differentially expressed (DE) by RNA-Seq. RT-qPCR confirmed that four miRNAs are significantly downregulated in UC compared to healthy urothelial samples (miR-105a, miR-143, miR-181a, and miR-214). Principal component analysis and hierarchical cluster analysis showed separation between miRNAs in iUC and the control group. The DE miRNAs are most often associated with gene silencing by miRNA, miRNAs in cancer, and miRNAs involved in DNA damage responses. Proteins involved include HRAS, KRAS, ARAF, RAF1, MAPK1, MAP2K1, MAPK3, FGFR3, EGFR, HBEGF, RASSF1, E2F2, E2F3, ERBB2, SRC, MMP1, and UP3KA. The differential expression of miRNAs in canine iUC compared to normal canine urothelial tissue indicates that these markers should be further evaluated for their potential role as diagnostic and therapeutic targets.
A 2-year-old, male neutered German Shepherd dog presented to his referring veterinarian with a history of blood noted in food when he was eating. Upon evaluation, a 4-cm proliferative mass located medial to the upper left fourth premolar on the hard palate was found. No other significant findings were noted upon
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