Ko Nakashima

Human enteropathy‐associated T‐cell lymphoma (EATL) is a rare primary aggressive intestinal T‐cell lymphoma associated with celiac disease and is considered to be a neoplasm of intraepithelial lymphocytes (IELs) with an innate lymphoid cell (ILC)‐like immunophenotype. The lack of an animal model has delayed the elucidation of its pathogenesis. In dogs, the histopathological and immunophenotypic features of intestinal large T‐cell lymphoma (ILTCL) are similar to EATL; however, its cell of origin remains unclear. We herein performed detailed immunophenotyping, an RNA expression analysis of selected genes, and gene mutation analysis of 54 cases of ILTCL, including 27 with fresh frozen samples available and 21 of intestinal small T‐cell lymphoma (ISTCL) in dogs. Canine ILTCL was characterised by the expression of cytotoxic granules (53/54) and frequent absence of CD4/CD8 (26/27) and T‐cell receptors (14/27). The mRNA expression of CD103 (25/35) and NKp46 (15/35) was detected in ILTCL by RNA in situ hybridisation. The gene mutation analysis showed mutations in NFKBIA (ILTCL, 31/54; ISTCL, 10/21), including truncating mutations (ILTCL, 11/54; ISTCL, 3/21). Mutations in STAT3 SH2 were less frequent (ILTCL, 13/54; ISTCL, 3/21) and the hotspot JAK1 mutation of human EATL was not detected. Immunohistochemistry for p‐Stat3 showed STAT3 pathway activation in ILTCL cases. These results suggest that canine ILTCL is also a neoplasm of IEL with an ILC‐like immunophenotype and STAT3 pathway activation, and loss‐of‐function mutations in NF‐κB pathway inhibitors are associated with its neoplastic changes. Therefore, canine ILTCL has potential as a valuable model for investigating the pathogenesis of EATL.

Background: The factors affecting the quality of histopathologic specimens obtained via small intestinal endoscopic biopsy (SIEB) remain unclear. Hypothesis/Objectives: To identify factors related to the quality of histopathologic specimens obtained via SIEB. Animals: Histopathologic duodenal and ileal specimens were obtained from 116 dogs and 38 cats that underwent SIEB for diagnostic purposes. Methods: This retrospective study analyzed 3354 individual histopathologic specimens scored using the grading system of histopathologic adequacy (GSHA). A lower GSHA score indicates lower quality specimens. Univariate and multivariate ordinal logistic models were used to assess the relationship between the GSHA score of the specimens and various explanatory factors, including fixation method, biopsy forceps size, biopsy site, and histopathologic diagnosis. The generalized estimating equation method was used to account for the clustering of specimens among animals. Results: Multivariate models using the specimens showed that filter paper fixation of endoscopic samples resulted in a higher GSHA score than floating fixation in both dogs (ordinal odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.15–0.25) and cats (ordinal OR: 0.19; 95% CI: 0.13–0.29). In dogs, the scores were lower for duodenal specimens than for ileal specimens and for specimens obtained using smaller forceps. In cats, the scores were lower for ileal specimens than for duodenal specimens and for older animals. Conclusion and Clinical Importance: The quality of histopathologic specimens obtained via SIEB is influenced by the fixation method. Additionally, other factors differ between dogs and cats. These results contribute to improved SIEB practices in veterinary medicine.

Background: Gastrointestinal eosinophilic sclerosing fibroplasia (GESF) in cats presents as mass(es) associated with the gastrointestinal tract, mesentery, and abdominal lymph nodes. Hypothesis/Objectives: To report the clinicopathological findings, treatment, and outcome of cats with GESF. Animals: Sixty client-owned cats diagnosed with GESF. Methods: Retrospective review of medical records of cats with histopathologically confirmed GESF. Results: The median age was 5.4 years (interquartile range [IQR], 3.3-8.9.); 30% were Domestic Shorthairs and 12% were Domestic Longhair cats, with the most prevalent pedigree breeds being Ragdolls (25%), Exotic Shorthair (10%) and Persian (8%) cats. The median duration of clinical signs was 90 days (IQR, 17.5-247.0); the most common clinical signs were weight loss (60%), hyporexia/anorexia (55%), chronic vomiting (37%), lethargy (35%) and chronic diarrhea (27%). Masses were located in the small intestine (32%), stomach (27%), ileocolic junction (15%), colon (10%), lymph node (8%) and mesentery (8%) and 15% of cats had >1 mass. Eosinophilia was present in 50% and hypoalbuminemia in 28% of cats. The mass was removed surgically in 37% of cases. Most cats (98%) were treated with corticosteroids. Survival was not statistically different between cats treated with surgical resection and cats treated with medical therapy alone, 88% of the cats were still alive at the time of writing. Conclusions and Clinical Importance: GESF is an important differential diagnosis for abdominal masses in cats, and has a much better prognosis than previously reported.

Background Gallbladder mucocele (GBM) is a common biliary disorder in dogs that can be categorized into 6 types, but the value of this classification scheme remains unknown. Cholecystectomy is associated with high death rates and warrants additional interrogation. Objectives Investigate the clinical value of ultrasonographic diagnosis of type of GBM and identify prognostic factors in dogs with GBM undergoing cholecystectomy. Animals Two hundred sixteen dogs. Methods Retrospective cohort study. Dogs with GBM diagnosed from 2014 to 2019 at 6 veterinary referral hospitals in Asia. Ultrasonogram images were reviewed and a GBM type (ie, types I-VI) assigned. Results Dogs with GBM type V as compared to I (OR, 8.6; 95% CI, 2.6-27.8; P < .001) and III (OR, 10.0; 95% CI, 2.5-40.8; P = .001), and dogs with type VI compared to I (OR, 10.5; 95% CI, 1.8-61.2; P = .009) and III (OR, 12.3; 95% CI, 1.8-83.9; P = .01) were more likely to exhibit signs of biliary tract disease. Independent predictors of death after cholecystectomy included age (OR, 2.81; 95% CI, 1.41-5.59; P = .003) and intraoperative systolic blood pressure (SBP) nadir. There was an interaction between SBP nadir and gallbladder rupture; SBP nadir in dogs with (OR, 0.92; 95% CI, 0.89-0.94; P < .001) and without (OR, 0.88; 95% CI, 0.82-0.93; P < .001) gallbladder rupture. Conclusion and Clinical Importance Increasing developmental stage of GBM could be associated with an increased likelihood of biliary tract related clinical signs. Nadir SBP deserves further investigation as a prognostic or potentially modifiable variable, particularly in the presence of gallbladder rupture.

Case summary: A 10-year-old castrated male domestic shorthair cat presented with a 6 month history of diarrhoea that responded poorly to medical treatment. Ultrasonography revealed moderate thickening of the colonic wall (4.8 mm) and right colic and jejunal lymphadenomegalies. Endoscopic examination revealed partial circumferential narrowing of the transverse colon and friable colonic mucosa with multiple haemorrhagic regions. Histopathological and immunohistochemical examinations revealed a large number of Escherichia coli phagocytosed by periodic acid–Schiff-positive macrophages. Bacterial culture also yielded enrofloxacin-sensitive E coli. The cat was initially treated with prednisolone, which resulted in little improvement. Following histopathological examination and bacterial culture, treatment with enrofloxacin was commenced. Antibacterial therapy resulted in remission of the diarrhoea and an increase in body weight within 14 days. Relevance and novel information: Granulomatous colitis (GC) or histiocytic ulcerative colitis has been rarely described in cats. There has only been one previously published case study involving a cat, and the aetiology remains largely unknown. The current article describes the regression of E coli-related GC following antibacterial treatment in a cat. Clinical signs, histopathological appearance and response to enrofloxacin were similar to those in canine GC. The current findings suggest that E coli also plays an important role in the development of feline GC.

Biopsy samples of colorectal polyps were collected and examined from 67 Miniature Dachshund dogs (including 35 cases with an additional biopsy). Histopathologic diagnoses of the initial biopsy samples were “inflammatory polyp” in 52 cases (78%), “adenoma” in 10 cases (15%), and “adenocarcinoma” in 5 cases (8%). Eight of 10 cases (80%) diagnosed as adenoma also had inflammatory polyp lesions in the same specimen. A second biopsy was performed in 25 cases (48%) initially diagnosed with inflammatory polyp. Pathologic diagnoses for the second biopsy were inflammatory polyp in 11 cases (44%), adenoma in 9 cases (36%), and adenocarcinoma in 5 cases (20%). The number of beta-catenin-positive nuclei in epithelial cells was significantly higher in adenoma (46%) and adenocarcinoma (75%) as compared with inflammatory polyp (6%). Normal epithelial cells and hyperplastic goblet cells in inflammatory polyps showed homogeneous positive cytoplasmic immunoreactivity for adenomatous polyposis coli (APC) antigen. However, APC expression was decreased in areas of intense nuclear beta-catenin expression in adenoma and adenocarcinoma lesions. Foci of cytokeratin 5/6–positive squamous cell-like neoplastic cells showed intense beta-catenin nuclear expression that was similar to squamous morules described in human colorectal tumors. The results of the present study suggest that the inflammatory polyp in Miniature Dachshunds is a progressive disease that may develop into adenoma and/or adenocarcinoma. In addition, immunohistochemical findings suggest that aberrations of APC and beta-catenin expression may be involved in tumor development within the inflammatory polyp lesions.

Intestinal T‐cell lymphoma is being more frequently diagnosed in dogs owing to the wide availability of endoscopy and clonality analysis in veterinary medicine. However, no epidemiological study on intestinal T‐cell lymphoma has been previously performed, and hence, information about dog breed, age and sex distributions of intestinal T‐cell lymphoma has largely remained unclear. In this study, breed predisposition to canine intestinal T‐cell lymphoma was determined by calculating odds ratios and 95% confidential intervals. Of the 43 breeds identified, 7 appeared to have an increased risk of developing intestinal T‐cell lymphoma, including Shiba dogs, German shepherds, Cairn terriers, Boston terriers, Papillons, Pugs and Maltese. Immunohistochemistry of representative Shiba cases revealed ubiquitous cytotoxic immunophenotype in both large and small cell lymphomas. Interestingly, CD20 co‐expression was observed in 11% of cases. It could potentially be aberrant expression of CD20 or neoplastic transformation of a normal subset of CD20‐positive T‐cells. A comparison of mean age between representative breeds revealed that Shiba dogs were slightly younger than Miniature Dachshunds (P < .05). However, there was no difference in survival between the 2 breeds. As Shiba dogs are predisposed to chronic enteropathy, there may be underlying inflammatory process contributing to lymphomagenesis of intestinal T‐cell lymphoma in this breed. Our findings provide insights into the underlying pathogenesis of breed‐specific canine intestinal T‐cell lymphoma.

Molecular clonality analysis of T-cell receptor (TCR) genes for diagnosing T-cell lymphoma is widely used in veterinary medicine. However, differentiating chronic enteritis (CE) from intestinal lymphoma is challenging because of the incompatibility between histopathologic and clonality analysis results. On the basis of findings that canine intestinal T-cell lymphoma and celiac disease share some common features, we conducted serologic examinations in combination with histopathologic and T-cell receptor clonality analyses in 48 dogs diagnosed with either CE or intestinal lymphoma. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against gliadin and tissue transglutaminase (tTG) were quantitatively measured using ELISA. The conditions were classified according to the histopathologic diagnosis, clonality analysis, and combined histopathologic/clonality analysis. Histopathologic analysis showed that dogs with intestinal lymphoma were likely to have high levels of serum IgA antibodies against gliadin and tTG, and serum IgG antibodies against tTG. No correlation between the diagnosed groups and control group was observed in the results of the clonality analysis and histopathologic/clonality analysis. It is interesting that dogs with intestinal lymphoma had a higher serum IgA titer against gliadin and tTG than did dogs with CE. These results suggest an association between repetitive inflammatory stimulation by gliadin peptides and subsequent intestinal lymphoma in dogs.