A case of Exophiala dermatitidis-induced phaeohyphomycosis in a cat with multiple intra-abdominal masses.

Pus discharge containing black granular materials (1-2 mm in diameter) was found in the abdominal skin of a 13-year-old sterilized female cat. Abdominal ultrasonography revealed a large intra-abdominal mass with abundant blood flow beneath the skin lesion. Laparotomy revealed a large mass that adhered to the spleen and left kidney. Similar small lesions were found in the abdominal wall and mesentery. The masses were surgically removed along with the spleen and kidney. Histopathologically, the mass lesions consisted of granulomas with lesional pigmented fungi, and the cat was diagnosed with phaeohyphomycosis. Uisng genetic analysis, the Exophiala dermatitidis was identified as the causative pathogen.

Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma.

Although chemotherapy using CHOP-based protocol induces remission in most cases of canine multicentric high-grade B-cell lymphoma (mhBCL), some cases develop early relapse during the first induction protocol. In this study, we examined the gene expression profiles of canine mhBCL before chemotherapy and investigated their associations with early relapse during the first whole CHOP-based protocol. Twenty-five cases of mhBCL treated with CHOP-based protocol as first induction chemotherapy were included in this study. Sixteen cases completed the first whole CHOP-based protocol without relapse (S-group), and nine developed relapse during the chemotherapy (R-group). RNA-seq was performed on samples from neoplastic lymph nodes. Differentially expressed genes (DEGs) were extracted by the comparison of gene expression profiles between S- and R-groups, and the differences in the expression levels of these genes were validated by RT-qPCR. Extracted 179 DEGs included the genes related to chemokine CC motif ligand, T-cell receptor signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway. We focused on chemokine CC motif ligand, and CCL4 was confirmed to be significantly downregulated in the R-group (P=0.039). We also focused on the genes related to T-cell signaling pathway, and CD3E (P=0.039), ITK (P=0.023), and LAT (P=0.023) genes were confirmed to be significantly upregulated in the R-group. The current results suggest that both changes in tumor cells and the interactions between tumor cells and immune cells are associated with the efficacy of the chemotherapy for first remission induction.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Diagnosis of severe fever with thrombocytopenia syndrome (SFTS) in a cat with clinical findings resembling lymphoma.

A two-year-old male domestic cat showed lethargy, tonic-clonic convulsion, and mucosal jaundice. Upon admission, blood examination indicated severe neutropenia and thrombocytopenia, and ultrasonography revealed diffuse splenomegaly with a honeycomb appearance and abdominal lymph nodes enlargement in addition to a decrease in cardiac blood flow indicating a shock condition. Cytology of the spleen showed a cell population composed of immature large lymphoid cells with distinct nucleoli, suggesting lymphoma. The cat received symptomatic treatments but died four hours later. Reverse transcriptase polymerase chain reaction assay of the spleen sample indicated the presence of severe fever with thrombocytopenia syndrome (SFTS) virus S gene segment. Clinical features of this case that was diagnose as SFTS were similar to lymphoma. Therefore, pet owners and veterinary workers should be protected against infection of SFTS.

Immunohistochemical features of canine ovarian papillary adenocarcinoma and utility of cell block technique for detecting neoplastic cells in body cavity effusions.

Dogs with ovarian papillary adenocarcinoma occasionally present with ascites and/or pleural effusion. These aspirated fluids often contain a large number of cells, and distinction between neoplastic cells and activated mesothelial cells can be difficult. In this study, 7 cases of canine ovarian papillary adenocarcinoma, including 3 with ascites and pleural effusion, were immunohistochemically examined. Ovarian tumor cells were positive for cytokeratin CAM5.2 (CAM5.2), Wilms' tumor 1 (WT-1) and progesterone receptor (PR) in all 7 cases. A metastatic lesion of the mediastinum in one case was also positive for CAM5.2, WT-1 and PR. Immunohistochemistry on cell blocks obtained from ascites and/or pleural effusion of 2 cases revealed the presence of PR-positive epithelial cells. Whereas, activated mesothelial cells in ascites or pleural effusion collected from dogs without neoplastic lesions were negative for PR. In addition, surface epithelium and subsurface epithelial structures (SES) of normal canine ovaries, that are considered to be the cell of origin for ovarian papillary adenocarcinoma, were also positive for CAM5.2, WT-1 and PR. These results indicate that, together with CAM5.2, WT-1 and PR is a useful diagnostic marker for canine ovarian papillary adenocarcinoma. Expression of PR may be associated with progesterone-dependent nature of canine ovarian papillary adenocarcinoma.

Outcomes and prognostic factors in canine epitheliotropic and nonepitheliotropic cutaneous T-cell lymphomas.

Canine cutaneous lymphoma is an uncommon lymphoma in dogs. Most canine cutaneous lymphoma cases have a T-cell origin. Canine cutaneous T-cell lymphoma (CTCL) is classified into epitheliotropic and nonepitheliotropic cutaneous lymphomas, and each type of lymphoma is subclassified into several histological subtypes. Limited information is available regarding the prognostic significance of clinical variables and histopathological subtypes in dogs with CTCL. This retrospective study aimed to investigate the influence of clinical variables and histopathological subtypes on the prognosis of dogs with CTCL. Forty-six dogs diagnosed with CTCL by histopathological examination were included. Histopathological specimens were reexamined and classified into CTCL subtypes. The influence of the type of skin lesion, histopathological subtype, haematological examination results and treatment response on the overall survival time (OS) was examined. Thirty-one dogs were diagnosed with epitheliotropic CTCL (mycosis fungoides in 28 dogs; pagetoid reticulosis in 3 dogs) and 15 dogs were diagnosed with nonepitheliotropic CTCL (anaplastic large T-cell lymphoma in 6 dogs; peripheral T-cell lymphoma, not otherwise specified, in 9 dogs). The OS of dogs diagnosed with epitheliotropic CTCL (141 days) was significantly shorter than that of dogs diagnosed with nonepitheliotropic CTCL (374 days). As clinical variables, the presence of neoplastic lymphocytes in peripheral blood, thrombocytopenia and initial chemotherapeutic response was related to prognosis. Our results demonstrated that histopathological subtype and several clinical variables were found to influence the prognosis of dogs with CTCL.

Prognostic factors for dogs with surgically resected gastrointestinal stromal tumors.

Few reports have investigated prognosis of canine gastrointestinal stromal tumor (GIST) cases treated by surgical resection alone. In the present study, we investigated the overall survival (OS) and prognostic factors for dogs with GIST treated by surgical complete resection alone. Fifty-three dogs were included, and the median OS was 18 months. Multivariate analysis showed that primary tumors in small intestine (P=0.04) is significantly associated with shorter OS, and median OS of the cases with cecum lesion and those with small intestine lesion was 22 and 6 months, respectively. The present study suggested primary tumor site was a novel prognostic factor for dogs with GIST treated by surgical complete resection alone.

Temporal deterioration of neurological symptoms and increase of serum acetylcholine receptor antibody levels after thymectomy: a case report of a cat with myasthenia gravis.

Neurological signs and serum acetylcholine receptor antibody (AChR-Ab) levels before and after thymectomy were monitored in a 6-year-old male cat with acquired Myasthenia Gravis (MG) as a paraneoplastic syndrome of thymoma. Soon after surgery, the neurological symptoms relapsed, and the cholinesterase inhibitor was administered to control them. The AChR-Ab levels increased postoperatively until 90 days after surgery. This is the first report on long term measurements of serum AChR-Ab levels in a cat with MG. Although thymectomy is valuable for the removal of thymoma, it may not resolve MG symptoms, neurological signs and serum AChR-Ab levels, without medication early after surgery. Also, this case report indicates that the AChR-Ab level might be a guide to detect a deterioration of MG symptoms.

Imatinib mesylate treatment in a dog with gastrointestinal stromal tumors with a c-kit mutation.

A 13-year-old spayed mixed-breed dog was diagnosed with a gastrointestinal stromal tumor (GIST) after histopathological examination of an abdominal mass. Five months after surgical resection of the tumor, we detected the recurrence of GIST with multiple disseminated abdominal lesions. A sequence analysis of cDNA obtained from a biopsy of the recurrent tumors revealed a mutation within exon 9 of the c-kit gene (1523A>T, Asn(508)Ile), which has been shown to cause ligand-independent phosphorylation of the KIT protein in GISTs and canine mast cell tumors (MCTs). Upon detection of the recurrent tumors, we initiated treatment with imatinib mesylate (10 mg/kg, q 24 hr). After 2 months, the dog achieved complete remission. Our findings indicate that canine GIST, and possibly MCT, may be responsive to molecular-targeted therapy.

A feline case of hepatic neuroendocrine carcinoma with gastrin immunoreactivity.

A 5-year-old castrated Japanese domestic cat was presented with persistent vomiting. Ultrasound examinations revealed many masses only in the liver, and the fine needle aspiration was performed. Cytologically, polygonal or oval shaped tumor cells forming rosette and cord-like patterns were demonstrated, and then, the hepatic lesions were diagnosed as neuroendocrine carcinoma tentatively. The cat died one month after admission and was necropsied. Histopathologically, the tumor cells of the hepatic mass were arranged in typical rosette and cord-like structures. They were considerably uniform in size with hyperchromatic round nuclei and eosinophilic cytoplasm. Most of tumor cells were immunopositive for chromogranin A, and some were positive for gastrin. The findings indicate the possibility that the present case was a gastrin-producing neuroendocrine carcinoma.

A case of canine multiple inflammatory colorectal polyps treated by endoscopic polypectomy and argon plasma coagulation.

Endoscopic polypectomy and argon plasma coagulation (APC) were performed in a refractory case of inflammatory colorectal polyps in a 7-year-old male Miniature Dachshund. Colonoscopic examination revealed a large sessile polyp and multiple diffuse small polyps, localized to the descending colon and rectum. The case showed a poor therapeutic response to prednisolone and cyclosporine. Under anesthesia, piecemeal resections were performed by polypectomy. APC was carried out to cauterize the polyp remnants. After treatment, reduction of the lesions and the improvement in clinical signs were observed, without recurrence of lesions for at least 10 months. Endoscopic treatment by polypectomy and APC is suggested to be a therapeutic option for refractory cases of inflammatory colorectal polyps in dogs.

Feline digital phaeohyphomycosis due to Exophiala jeanselmei.

The black nodule measuring 1 cm in diameter developed in the base of nail of an 8-year-old Japanese domestic male cat. Histological examination of the excised nodule revealed a granulomatous lesion extending from the epidermis to adjacent bone. The lesion was consisted of diffuse infiltration of macrophages with epithelioid cells and multinucleated giant cells. These macrophages contained a few to numerous yeast-like brown pigmented fungus cells with a spherical shape and dark thick wall. The PCR amplification with universal primers of the 28S ribosomal RNA gene yielded a 628-bp fragment and the direct sequence confirmed that the diagnosis of the lesion was phaeohyphomycosis caused by the pathogenic dematiaceous fungus, Exophiala jeanselmei.