Periocular fibrosarcoma with lipogranulomatous conjunctivitis in a cat.

A 9-year-old, female spayed domestic short-haired cat was presented with a 4-year history of bilateral lipogranulomatous conjunctivitis (LGC), which was confirmed via histopathology. Thirteen months following the initial biopsy, the cat was presented with a rapidly progressive mass lesion of the palpebral conjunctiva of the right eye. A surgical debulking, followed 1 month later by exenteration after marked regrowth of the mass confirmed fibrosarcoma. This case report is the first to describe a cat with chronic bilateral LGC that later developed a unilateral fibrosarcoma within the eyelid tissue of the right eye. Fibrosarcoma should be considered a differential in any cat with chronic LGC that develops a rapidly progressive mass in the eyelid.

Thymidine Kinase Type 1 and C-Reactive Protein Concentrations in Dogs with Spontaneously Occurring Cancer.

BACKGROUND: Serum thymidine kinase type 1 (TK1) and canine C-Reactive Protein (cCRP) might be useful in detecting dogs with cancer. Algorithms combining biomarkers are sometimes more accurate than results of individual tests. OBJECTIVES: The aim of this study was to compare serum TK1 and cCRP and Neoplasia Index (NI) in healthy and tumor-bearing dogs. ANIMALS: Client-owned dogs with (n = 253) and without (n = 156) cancer. METHODS: Retrospective case-control study. Dogs with cancer were identified after submission of samples for commercial assay and case details were retrospectively collected. Healthy dogs (control) were identified through breed groups and health status was confirmed by health questionnaire for a minimum of 6 months. Serum TK1 activity was measured using a quantitative chemiluminescent assay and serum cCRP was measured using a quantitative ELISA assay. RESULTS: TK1 activity in the cancer (n = 253) and control group (n = 156) were 7.0 µ/L (median, range <0.5 to >100) and 1.8 µ/L (median, range 0.4 to 55.3), respectively (P < .001). cCRP concentrations in the cancer and control group were 6.0 mg/L (median, range <0.5 to >50) and 1.6 mg/L (median, range 0.09 to >50), respectively (P < .001). The NI in the cancer and control group were 6.4 (median, range 0-9.9) and 0.9 (median, range 0-7.6), respectively (P < .001). ROC AUCs of the NI and TK1 for all cancers were greater than 0.8, highest for lymphoma and histiocytic sarcoma. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased concentrations of TK1 and cCRP, when present in dogs with cancer, might be useful in confirming a diagnosis and monitoring response to treatment.

Evaluation of a combination chemotherapy protocol including lomustine and doxorubicin in canine histiocytic sarcoma.

OBJECTIVES: To describe a chemotherapy protocol combining lomustine and doxorubicin in canine histiocytic sarcoma, including outcomes and toxicity. MATERIALS AND METHODS: Retrospective review of case records for dogs with histiocytic sarcoma treated with lomustine and doxorubicin (± cyclophosphamide) alternating every 2 weeks. Data collected included signalment, clinical signs, clinicopathological abnormalities, extent of disease, response, toxicity, time to tumour progression and survival time. RESULTS: Of 17 dogs, 15 had disseminated or metastatic disease. The median number of chemotherapy cycles (one dose of each drug) received was three; most dogs discontinued therapy due to progressive disease. Dose reductions or delays occurred in 18% of cycles. The overall response rate was 58%, with a median time to tumour progression of 185 (range, 59 to 268) days for responders. The overall median survival time was 185 (18 to 402) days. No significant prognostic factors were identified. CLINICAL SIGNIFICANCE: The protocol appeared well-tolerated, had some efficacy against canine histiocytic sarcoma in the study population and could be considered as an alternative to single-agent protocols; prospective comparison may be warranted.

Applicability of 3T body MRI in assessment of nonfocal bone marrow involvement of hematopoietic neoplasia in dogs.

BACKGROUND: The utility of whole body magnetic resonance imaging (MRI) in detecting bone marrow infiltration in dogs with cancer has not been investigated. OBJECTIVES: To assess the feasibility of 3T body MRI for bone marrow assessment in dogs with hematopoietic neoplasia. ANIMALS: Seven dogs with B-cell lymphoma, 3 dogs with myelodysplastic syndrome (MDS), and 2 clinically normal dogs. METHODS: A prospective study of dogs with hematopoetic cancer was conducted using T1W, T2W, In-Phase, Out-of-Phase and STIR pulse sequences of the body excluding the head prior to bone marrow sampling. The relative signal intensity of a midlumbar vertebral body and a midshaft femoral bone marrow was compared by visual and point region of interest analysis to regional skeletal muscle. RESULTS: Similarity of femoral diaphyseal and vertebral body marrow signal intensity to that of skeletal muscle on the Out-of-Phase sequence was useful in distinguishing the 3 dogs with hypercellular marrow because of MDS from the 7 dogs with B-cell lymphoma and from the 2 clinically normal dogs. 1/7 dogs with lymphoma had proven bone marrow involvement but normal cellularity and less than 5% abnormal cells. Unaffected midfemoral marrow had greater signal intensity than skeletal muscle and unaffected vertebral marrow had less signal intensity than skeletal muscle on the Out-of-Phase sequence. CONCLUSIONS AND CLINICAL IMPORTANCE: 3T, Out-of-Phase MR pulse sequence was useful in distinguishing diffuse bone marrow infiltrate (MDS) from minimally or unaffected marrow using skeletal muscle for signal intensity comparison on whole body MRI.

Molecular profiling reveals prognostically significant subtypes of canine lymphoma.

We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.

Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma.

BACKGROUND: Idarubicin, a PO bioavailable anthracycline antibiotic-class chemotherapeutic, could have substantial convenience advantages over currently available similar class agents in use that require IV delivery. OBJECTIVES: The primary objective of this study was to determine the maximally tolerated dose (MTD), dose-limiting toxicities (DLTs), and basic pharmacokinetic parameters of oral idarubicin exposure in dogs with lymphoma after a single oral dose. A secondary objective was to document preliminary antitumor efficacy in an expanded treatment cohort using the established MTD. ANIMALS: Client-owned dogs with measurable lymphoma. METHODS: Dogs (n = 31) were enrolled in a prospective open label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose escalations were made with 3 dogs per dose level, and the MTD was established based on the number of patients experiencing a DLT. Plasma concentrations of idarubicin and idarubicinol were determined by postdose sampling. Assessment of antitumor efficacy focused on evaluation of accessible, measurable lymph nodes and skin lesions by modified RECIST guidelines. RESULTS: The MTD in dogs > 15 kg body weight was 22 mg/m(2) . Adverse hematologic events (neutropenia and thrombocytopenia) were the predominant DLT and generally correlated with higher plasma concentrations of idarubicin and idarubicinol. CONCLUSIONS AND CLINICAL IMPORTANCE: PO administered idarubicin was generally well-tolerated and had preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential clinical advantage of a safe and efficacious oral anthracycline alternative supports further investigations of this agent in repeated-dose, randomized clinical trials.

A tumor-related lymphoid progenitor population supports hierarchical tumor organization in canine B-cell lymphoma.

BACKGROUND: Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor-initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B-cell lymphoma have not been conclusively identified. HYPOTHESIS/OBJECTIVES: Tumor cells with a progenitor phenotype exist in B-cell lymphoma, reflecting a hierarchical organization. ANIMALS: Twenty-eight client-owned dogs with previously untreated B-cell lymphoma and 6 healthy dogs. METHODS: This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B-cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL-2Rγ(-/-) mice was adapted to expand and serially transplant primary canine B-cell lymphoma. RESULTS: LPCs were expanded in lymph nodes from 28 dogs with B-cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B-cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest the presence of a hierarchy of tumor cells in B-cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy.