Feline restrictive orbital myofibroblastic sarcoma treated with toceranib phosphate (Palladia) as adjuvant chemotherapy: A case study of one cat.

Key Clinical Message: This is the first case report of treatment with toceranib phosphate as postsurgical adjuvant chemotherapy for advanced FROMS. This reported case highlights the need for further studies on the efficacy of toceranib phosphate as adjuvant chemotherapy for FROMS. Abstract: Feline restrictive orbital myofibroblastic sarcoma (FROMS) is a rare aggressive tumor in cats. We explored the effectiveness of using toceranib phosphate as postsurgical adjuvant chemotherapy for advanced FROMS in a 7-year-old cat. Despite treatment, the cat died 4 months after surgery. This report highlights the need for further studies on the efficacy of toceranib phosphate as adjuvant chemotherapy for FROMS.

Intratumoral heterogeneity of c-KIT mutations in a feline splenic mast cell tumor and their functional effects on cell proliferation.

A cat was presented with mast cell tumors (MCTs) of the skin and spleen. During the initial diagnosis, the exon 8 mutation of c-KIT was detected in the masses from skin and spleen by a commercial laboratory test. Consequently, treatment with toceranib was started. After complete remission, because of recurrence on day 117, the spleen and skin tumors were removed, but the cat eventually died on day 191. The analysis of ten cDNA clones of the c-KIT gene cloned from the surgically removed spleen revealed that seven different cDNA patterns were included, indicating the heterogeneity of this gene in the splenic MCT. The seven cDNA nucleotide patterns can be classified into four protein sequence patterns. In addition to the previously known mutations in exon 8, we identified novel mutations in exons 9, 10, and 18; four amino acids deletion in exon 9, and a point mutation in exons 10 and 18. Mouse IL-3-dependent cell line, Ba/F3, was transduced with these mutant clones, and c-KIT phosphorylation and proliferation assays were performed. We found that certain mutations affected the c-KIT phosphorylation status and cell proliferation. This suggests that heterogeneity among the population of tumor cells exists in MCTs, and that the dominant clones of this heterogeneity may contribute to the subsequent tumor cell growth.

Outcome of appendicular or scapular osteosarcoma treated by limb amputation in cats: 67 cases (1997-2018).

OBJECTIVE: To evaluate the metastasis rate, survival time, and prognostic factors associated with appendicular or scapular osteosarcoma treated by limb amputation in cats. ANIMALS: 67 cats with histologically confirmed appendicular or scapular osteosarcoma treated by limb amputation. PROCEDURES: This retrospective cohort study included cats with histologically confirmed appendicular or scapular osteosarcoma between January 1997 and December 2018. A questionnaire survey was conducted at veterinary clinics where limb amputation was performed. Distant metastasis, local recurrence, and lymph node metastasis rates and survival time were determined. Factors associated with distant metastasis and survival were investigated. RESULTS: The distant metastasis rate after limb amputation was 41.9% (26/62). The overall distant metastasis rate was 46.3% (31/67), including 5 cats with distant metastasis at the time of amputation. Osteosarcoma of the humerus resulted in distant metastasis in 6 of 7 cases. Osteosarcoma of the humerus was significantly associated with distant metastasis in univariate and multivariate analyses (adjusted OR, 9.56). The rate of lymph node metastasis after limb amputation was 3.0% (2/66), and the local recurrence rate was 9.0% (6/67). The median survival time was 527 days. Age and tumor location were not significantly associated with survival time. CLINICAL RELEVANCE: Distant metastasis occurs in approximately 40% of cats with appendicular or scapular osteosarcoma after limb amputation. In addition, osteosarcoma of the humerus has a particularly high incidence of distant metastasis. Detailed follow-up is therefore necessary, even after limb amputation, especially in cases of osteosarcoma of the humerus.

Bimodal immunoglobulin A gammopathy in a cat with feline myeloma-related disorders.

A 10-year-old female spayed mixed breed cat with a subcutaneous mass on the right hind limb was revealed with bimodal monoclonal gammopathy composed of IgA by immunoelectrophoresis and immunofixation. Approximately 1 month after referral, the cat died due to renal failure. Postmortem immunohistopathologic evaluation of the subcutaneous mass revealed neoplastic cell proliferation of plasma cells and giant myeloma cells. Neoplastic cells were also present in the liver and spleen. These results led to the diagnosis of a rare case of feline myeloma-related disorders with extramedullary plasmacytoma infiltrating in multiple locations. This report emphasizes the necessity to accumulate cases with similar clinicopathologic findings in the future.

A case of feline systemic reactive angioendotheliomatosis.

A 3-year-old domestic shorthair cat presented with lethargy and anorexia. A blood test showed regenerative anaemia and thrombocytopenia. Thoracic radiographs showed a small amount of pleural effusion. The cat did not respond to treatment and died on the fifth day. Necropsy revealed moderate pericardial effusion, and multifocal coalescing haemorrhages were observed on both atria. Histological analysis revealed that the most severe lesions were located on the heart. Numerous arterioles supplying the heart were partially to completely filled with plump spindle cells that often formed glomerulus-like arrangements within the lumen. Similar vascular proliferative lesions were also found in the liver, pancreas and kidney. Immunohistochemical analysis showed that these intraluminal proliferative spindle cells were positive for anti-von Willebrand factor (vWF). Strongly positive antismooth muscle actin staining was observed at the periphery of these intraluminal proliferations (comprising arteriolar smooth muscle) and certain intraluminal cells (pericytes). The intraluminal thrombi were also positive for vWF. Those thrombi were confirmed as platelet thrombi by phosphotungstic acid haematoxylin and Masson's trichrome staining. These results were consistent with feline systemic reactive angioendotheliomatosis.

Immunohistochemical evaluation of canine ovarian cysts.

To clarify the immunohistochemical characteristics of canine ovarian cysts, 109 canine ovarian cysts (57 cysts of subsurface epithelial structures: SES, 26 graafian follicle cysts, 12 cystic rete ovarii and 14 cysts difficult to classify morphologically) were examined regarding their lining cells immunohistochemically using antibodies against placental alkaline phosphatase (PLAP), S100, inhibin alpha, desmin and AE1/AE3. Both cysts of SES and cystic rete ovarii had a positive immunoreaction to desmin and AE1/AE3, whereas all cysts all but graafian follicle cysts were negative for inhibin alpha. PLAP-positive immunoreaction was observed only in cysts of SES. Graafian follicle cysts had a positive immunoreaction to inhibin alpha, but were negative for PLAP, desmin and AE1/AE3. Fourteen cysts were difficult to classify morphologically because these cysts had single-squamous lining cells and lacked other morphological characteristics. However, these unclassified cysts were immunohistochemically divided into two groups, including positive and negative cysts, by the reactivity of PLAP. The PLAP-positive cysts were considered large cysts of SES. These results suggest that PLAP was a useful marker for classification of cysts of SES, although cysts originating from SES are not always positive for this antigen.

Immunohistochemical evaluation of canine ovarian tumors.

Canine ovarian tumors (epithelial tumor, sex-cord stromal tumor, germ cell tumor) classifying into 9 histological types were examined immunohistochemically using placental alkaline phosphatase (PLAP), cytokeratin7 (CK7), desmin, S100, AE1/AE3, inhibin alpha, vimentin, and alfa feto-protein (AFP). The papillary and tubular types observed in epithelial tumors were immunoreactive for desmin and AE1/AE3. The papillary type was also immunoreactive for PLAP and CK7. The solid type, nest type, cord type, palisade type, cystic type and spindle type, which were observed in sex-cord stromal tumors, showed a positive immunoreaction for S100 but little or no positive immunoreaction for inhibin alpha with an exception of positive result in the palisade type. Most of the sex-cord stromal tumors were AE1/AE3-positive except for the palisade type. In the cobblestone type observed in germ cell tumors, only vimentin and AFP were positive. The present study elucidated the detailed histological and immunohistochemical characteristics of canine ovarian tumors.

Expression of monocarboxylate transporter 1 (MCT1) in the dog intestine.

In this study, the expression and distribution of monocarboxyolate transporter 1 (MCT1) along the intestines (duodenum, jejunum, ileum, cecum, colon and rectum) of dogs were investigated at both the mRNA and protein levels. The expression of MCT1 protein and its distribution were confirmed by Western blotting and immunohistochemical staining using the antibody for MCT1. We identified mRNA coding for MCT1 and a 43-kDa band of MCT1 protein in all regions from the duodenum to the rectum. Immunoreactive staining for MCT1 was also observed in epithelial cells throughout the intestines. MCT1 immunoreactivity was greater in the large intestine than in the small intestine. MCT1 protein was predominantly expressed on the basolateral membranes along intestinal epithelial cells, suggesting that MCT1 may play an important role in lactate efflux and transport of short-chain fatty acids (SCFAs) to the bloodstream across the basolateral membranes of the dog intestine.