Activation of the Wnt/ß-catenin signaling pathway and CTNNB1 mutations in canine intestinal epithelial proliferative lesions.

Nuclear expression of ß-catenin has been reported in canine intestinal epithelial tumors (IETs) and colorectal inflammatory polyps (CIPs) with dysplastic epithelia. However, the role of the Wnt/ß-catenin signaling pathway in these lesions remains unclear. To investigate the association between the nuclear ß-catenin expression and the activation of the Wnt/ß-catenin signaling pathway, immunohistochemistry and mutation analyses were conducted on 64 IETs and 20 CIPs. IETs and CIPs with ß-catenin nuclear and/or cytoplasm immunolabeling were classified as ß-catenin (+). The immunostaining scores of c-Myc and Cyclin D1 and Ki-67 index were significantly higher in ß-catenin (+) cases than in ß-catenin (-) cases. Identical APC mutations (p.E154D and p.K155X) were detected in 6/41 ß-catenin (+) IETs; all 6 of IETs with APC mutations were Jack Russell Terriers. CTNNB1 mutations were detected in 29/42 ß-catenin (+) IETs, 3/11 ß-catenin (+) CIPs, and 2/22 ß-catenin (-) IETs, most of which were hotspots associated with human colorectal carcinoma. In one Miniature Dachshund diagnosed with a CIP that subsequently developed into an IET, the same CTNNB1 mutation was detected in both lesions. The immunohistochemical results suggest that cell proliferative activity in ß-catenin (+) cases may be associated with activation of the Wnt/ß-catenin signaling pathway. The mutation analysis results suggest that CTNNB1 mutations may be associated with cytoplasmic ß-catenin accumulation in IET and CIP. Furthermore, the dysplastic epithelium in CIP may progress to IET through the activation of the Wnt/ß-catenin signaling pathway by the CTNNB1 mutation.

Enzootic bovine leukosis caused by bovine leukemia virus classified as Group C based on viral whole genome sequencing in a 23-month-old Holstein-Friesian heifer.

A 23-month-old Holstein-Friesian heifer presented with inactivity and diarrhea. On physical examination, no enlargement of superficial lymph nodes was observed. Hematological examination revealed lymphocytosis. The bovine leukemia virus (BLV) proviral load was 2,122 copies/10 ng DNA, and BLV was classified as Group C based on whole genome phylogenetic analysis. Monoclonal proliferation of B-cells and monoclonal integration of the BLV provirus in the bovine genome were detected by a clonality test of B-cells and inverse PCR, respectively. Although lymph nodes were not swollen at necropsy, histopathological examination revealed neoplastic lymphocyte proliferation in lymph nodes, which were immune positive for CD5 and CD20, and negative for CD3. The heifer was diagnosed with EBL caused by BLV classified as Group C.

Primary pulmonary diffuse large B-cell lymphoma associated with feline leukaemia virus infection in a young cat.

CASE SUMMARY: A 4-year-old castrated male domestic shorthair cat with a continuous cough was brought to a private veterinary clinic for detailed examination. Radiography of the thoracic cavity revealed a severe radiopaque region in the caudal lobe of the right lung. At 108 days after the initial visit, CT showed a mass of 27 × 23 × 18 mm in the caudal lobe of the right lung. At that time, no abnormalities in other organs except for the lung were detected on CT and peripheral blood and blood biochemistry tests. The mass in the caudal lobe of the right lung was resected by lobectomy; it had a white surface and was firm. Histopathologically, the mass was non-encapsulated, showing an unclear boundary with surrounding tissues. The mass comprised large, round or polygonal neoplastic cells arranged in a diffuse pattern. Immunohistochemically, neoplastic cells were diffusely positive for CD20, feline leukaemia virus (FeLV) p27 and FeLV glycoprotein 70 but negative for CD3, CD204 and E-cadherin. Based on these findings, diffuse large B-cell lymphoma associated with FeLV infection was diagnosed. Although the cat showed no clinical signs of gastrointestinal or respiratory injury, a routine ultrasonography revealed thickening in the jejunum wall 196 days after lobectomy, and subsequent fine-needle aspiration examination confirmed high-grade lymphoma. RELEVANCE AND NOVEL INFORMATION: This is the first report of primary pulmonary diffuse large B-cell lymphoma associated with FeLV infection in a young cat.