Clinical and histopathological classification of feline intraocular lymphoma.

This retrospective study aimed to describe and classify cats with intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared with ocular manifestations of multicentric disease and assess the clinical outcomes of these patients. One hundred seventy-two cases identified through biopsy submissions were reviewed histologically; 163 of these cases were subtyped according to the WHO classification system. Cases were categorized as having PSOL or ocular lymphoma with suspected systemic involvement (SSI) based on submission forms and follow-up data. The majority of cases exhibited concurrent uveitis (75%) and secondary glaucoma (58%). Diffuse large B-cell lymphoma was the most common subtype (n = 86; 53%), followed by peripheral T-cell lymphoma (n = 44; 27%). Other subtypes included anaplastic large T- (n = 8; 5%) and B-cell (n = 4; 2.5%) lymphomas, and 15 cases (9%) were negative for all immunohistochemical markers. In sixty-nine cases (40%), adequate clinical data and sufficient survival data were obtained to distinguish PSOL from SSI. PSOL comprised the majority of cases (64%), while 36% had SSI. When covarying for age at diagnosis, the median survival time was significantly higher (P = 0.003) for cases of PSOL (154 days) versus those with SSI (69 days); hazards ratio of 0.47 for PSOL (95% CI: 0.241-0.937). The subtype of lymphoma did not affect survival time. Cats with PSOL represent a greater proportion of the disease population, and this subset of cats with intraocular lymphoma has a better clinical outcome.

Clinical and pathological classification of canine intraocular lymphoma.

The objectives of this retrospective study of 100 dogs with intraocular lymphoma were to describe the histomorphologic and immunohistochemical features of canine intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared to multicentric disease, and assess the clinical outcomes of these patients. Selected cases from Penn Vet Diagnostic Laboratory and Comparative Ocular Pathology Lab of Wisconsin (2004-2015) were evaluated and subtyped using the WHO classification system. Peripheral T-cell lymphoma and diffuse large B-cell lymphoma were the two most common subtypes. Questionnaires were distributed to the referring veterinarians and veterinary ophthalmologists inquiring about clinical signs at time of enucleation, staging, patient outcome, treatment, and disease progression. Cases were categorized as PSOL if only ocular involvement was noted at the time of diagnosis based on the clinical staging criteria. The majority of cases (61%) did not have systemic involvement at the time of diagnosis, and these cases did not progress postoperatively. Median survival time (MST) was significantly higher for the presumed solitary intraocular cases: 769 vs. 103 days, hazard ratio of 0.23 (95% CI: 0.077-0.68). The subtype of lymphoma did not affect survival time. The results of this study suggest two significant points of clinical interest: the majority of dogs (61%) presented without signs of systemic involvement of lymphoma at the time of enucleation, and dogs with only ocular involvement showed no disease progression postenucleation.

Malignant transformation and subsequent leptomeningeal carcinomatosis of a gastric polyp in a dog.

Progressive carcinogenesis of a gastric polyp with transformation to gastric adenocarcinoma and subsequent development of leptomeningeal carcinomatosis is described in an adult male Scottish terrier. Presenting clinical signs consisted of vomiting with intermittent hematemesis. Surgical biopsies over the course of 14 months documented the progression from gastric polyp to minimally invasive gastric carcinoma to invasive gastric adenocarcinoma, a pathogenesis not previously documented in veterinary oncology. The patient ultimately developed neurologic pathology and was euthanized, and necropsy evaluation identified widespread carcinomatosis with accompanying leptomeningeal metastasis. As in humans, gastric polyps in dogs rarely have malignant potential.

Unique Presentations of Burkholderia gladioli Infections in Several Strains of Immunocompromised Mice.

Four strains of experimentally naïve mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ [NSG], NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ[NRG], B6.129S(Cg)-Stat1tm1Dlv/J [STAT1-/-], and B6.129S7-Ifngr1tm1Agt/J [IFNγR-/-] housed in a barrier facility developedunusual and seemingly unrelated clinical signs. Young NSG/NRG mice (n = 49, mean age = 4 ± 0.4 mo) exhibited nonspecificclinical signs of moderate-to-severe lethargy, hunched posture, decreased body condition, and pallor. In contrast to the NSG/NRGmice, the STAT1-/- and IFNγR-/-mice (n = 5) developed large subcutaneous abscesses on the head and neck. These micewere euthanized, and samples were collected for culture. NSG/NRG mice had moderate-markedly enlarged livers (20 of49, 40%) and spleens (17 of 49, 35%). The livers contained multiple, variably-sized, tan regions throughout all lobes. Histologyrevealed necrotizing hepatitis (13 of 17, 77%), splenic and hepatic extramedullary hematopoiesis (17 of 17, 100%), glomerularhistiocytosis (6 of 17, 35%), and metritis (6 of 11, 55%) with perivascular inflammation, suggesting hematogenous spreadDifferentials for these lesions included mouse hepatitis virus, ectromelia virus, Pseudomonas aeruginosa, Salmonella spp.,and Clostridium piliforme. Burkholderia gladioli was cultured from liver lesions and subcutaneous abscesses and confirmedwith 16S ribosomal RNA sequencing. After completing systematic testing of the environment, failure of the water autoclavecycle was suspected as the cause of the outbreak. To address the situation, individually ventilated racks were sanitized andnew breeders were purchased; these actions dramatically reduced B. gladioli infections. The current literature contains fewreports of B. gladioli infections in immunocompromised mice, and its typical presentation is torticollis and rolling. B. gladioliinfection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice.Careful monitoring of sterilization techniques is essential to prevent such infections in a barrier facility.

Hepatocytes demarcated by EphB2 contribute to the progression of nonalcoholic steatohepatitis.

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor 2 (EphB2). EphB2, acting as a downstream effector of Notch signaling in hepatocytes, was sufficient to induce cell-autonomous inflammation. Knockdown of Ephb2 in hepatocytes ameliorated inflammation and fibrosis in a mouse model of NASH. Thus, EphB2-expressing hepatocytes contribute to NASH progression and may serve as a potential therapeutic target.

Apocrine gland anal sac adenocarcinoma with perineural metastasis in a cat.

CASE SUMMARY: A 15-year-old female spayed domestic shorthair cat was presented for hyporexia and acute development of L4-Cd myelopathy (urinary incontinence, pelvic limb paresis with hyporeflexia and absent tail tone). Humane euthanasia was elected owing to the rapid neurological deterioration and necropsy was performed. Post-mortem examination identified a right-sided anal sac mass and medial iliac lymphadenopathy. No gross lesions were evident in the cauda equina or peripheral nerves. Histopathology and immunohistochemistry utilizing wide-spectrum cytokeratin confirmed apocrine gland carcinoma of the anal sac with lymph node, peripheral nerve and cauda equina metastasis. RELEVANCE AND NOVEL INFORMATION: This is the first report of feline anal sac adenocarcinoma metastasizing to perineural tissue. In addition, it provides a novel differential diagnosis for L4-Cd myelopathy and urinary incontinence in a cat.

Missing and delayed auditory responses in young and older children with autism spectrum disorders.

BACKGROUND: The development of left and right superior temporal gyrus (STG) 50 ms (M50) and 100 ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD + LI) (and perhaps concomitantly lower general cognitive abilities). METHODS: Thirty-five TD controls, 63 ASD without language impairment (ASD - LI), and 38 ASD + LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10 years old) and older groups (11-15 years old). RESULTS: Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD - LI and ASD + LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD + LI (90 versus 66%, p = 0.04), with no differences between TD and ASD - LI (90 versus 76%, p = 0.14) or between ASD - LI and ASD + LI (76 versus 66%, p = 0.53). In older subjects, whereas no differences were observed between TD and ASD + LI, responses were observed more often in ASD - LI than ASD + LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups. CONCLUSION: Although present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11 years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11 years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.

Maturational differences in thalamocortical white matter microstructure and auditory evoked response latencies in autism spectrum disorders.

White matter diffusion anisotropy in the acoustic radiations was characterized as a function of development in autistic and typically developing children. Auditory-evoked neuromagnetic fields were also recorded from the same individuals and the latency of the left and right middle latency superior temporal gyrus auditory ~50ms response (M50)(1) was measured. Group differences in structural and functional auditory measures were examined, as were group differences in associations between white matter pathways, M50 latency, and age. Acoustic radiation white matter fractional anisotropy did not differ between groups. Individuals with autism displayed a significant M50 latency delay. Only in typically developing controls, white matter fractional anisotropy increased with age and increased white matter anisotropy was associated with earlier M50 responses. M50 latency, however, decreased with age in both groups. Present findings thus indicate that although there is loss of a relationship between white matter structure and auditory cortex function in autism spectrum disorders, and although there are delayed auditory responses in individuals with autism than compared with age-matched controls, M50 latency nevertheless decreases as a function of age in autism, parallel to the observation in typically developing controls (although with an overall latency delay). To understand auditory latency delays in autism and changes in auditory responses as a function of age in controls and autism, studies examining white matter as well as other factors that influence auditory latency, such as synaptic transmission, are of interest.