Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane.

BACKGROUND: Lymphoma (LSA) is a common malignancy in dogs. Epigenetic changes are linked to LSA pathogenesis and poor prognosis in humans, and LSA pathogenesis in dogs. Sulforaphane (SFN), an epigenetic-targeting compound, has recently gained interest in relation to cancer prevention and therapy. OBJECTIVE: Examine the impact of oral supplementation with SFN on the lymph node proteome of dogs with multicentric LSA. ANIMALS: Seven client-owned dogs with multicentric LSA. METHODS: Prospective, nonrandomized, noncontrolled study in treatment-naïve dogs with intermediate or large cell multicentric LSA. Lymph node cell aspirates were obtained before and after 7 days of oral supplementation with SFN, and analyzed via label-free mass spectrometry, immunoblots, and Gene Set Enrichment Analysis. RESULTS: There was no clinical response and no adverse events attributed to SFN. For individual dogs, the expression of up to 650 proteins changed by at least 2-fold (range, 2-100) after supplementation with SFN. When all dogs where analyzed together, 14 proteins were significantly downregulated, and 10 proteins were significantly upregulated after supplementation with SFN (P < .05). Proteins and gene sets impacted by SFN were commonly involved in immunity, response to oxidative stress, gene transcription, apoptosis, protein transport, maturation and ubiquitination. CONCLUSIONS AND CLINICAL IMPORTANCE: Sulforaphane is associated with major changes in the proteome of neoplastic lymphocytes in dogs.

Nasal adenocarcinoma as a suspected secondary malignant neoplasm in a cat previously treated for nasal lymphoma.

CASE SUMMARY: A case of nasal adenocarcinoma as a suspected secondary malignant neoplasm following definitive radiation therapy and multiagent chemotherapy for nasal lymphoma is described. An 11-year-old spayed female domestic shorthair cat was presented for a 3-week history of progressive facial swelling located over the nasal planum and extending to the medial canthus of the right eye. The cat was previously diagnosed with nasal lymphoma and treated with chemotherapy and definitive radiation 2.5 years prior. Although a definitive diagnosis could not be obtained via cytology, recurrent lymphoma was suspected based on the cat's history and recurrent clinical signs. A lymphoma-directed chemotherapy protocol was attempted, but no clinical response was achieved. The cat was euthanased owing to progressive clinical signs and a diagnosis of nasal adenocarcinoma was made on necropsy examination. Both the original diagnosis of nasal lymphoma and the secondary diagnosis of nasal adenocarcinoma were confirmed with immunohistochemistry. RELEVANCE AND NOVEL INFORMATION: Secondary malignant neoplasm following radiation therapy is infrequently reported in the veterinary literature. In the few reports that exist, most have described sarcoma development in the dog following radiation therapy. In the present report, we describe a cat with a suspected radiation-induced nasal adenocarcinoma that developed 2.5 years after definitive radiation treatment for nasal lymphoma.

Cutaneous and subcutaneous metastasis of appendicular osteosarcoma in dogs: 20 cases.

BACKGROUND: Metastasis of appendicular osteosarcoma is most common to the lungs and is generally considered a terminal event in dogs. Behavior and prognosis associated with cutaneous or subcutaneous metastases (CSM) is poorly defined. OBJECTIVE: Describe the population and gather prognostic information regarding appendicular osteosarcoma with CSM in dogs. ANIMALS: Twenty dogs with appendicular osteosarcoma and CSM. METHODS: Retrospective case series. Medical records were searched to identify dogs diagnosed with appendicular osteosarcoma that developed CSM. Demographic data, order of metastatic events, and CSM clinical features were evaluated. Kaplan-Meier survival curves were constructed and log-rank tests were used to compare survival between groups of dogs. RESULTS: In 19 dogs (95%), CSM was an incidental finding. Seventeen dogs (85%) developed pulmonary metastasis, and 1 dog (5%) developed bone metastasis. No other metastatic sites were detected before euthanasia. The median CSM-free interval and CSM survival time were 160 days (range: 0-542 days) and 55 days (range: 5-336 days), respectively. The median CSM survival time was significantly longer for dogs treated with surgery and chemotherapy (94 days) or chemotherapy only (64 days) than for dogs that did not receive these treatments (11 days) (P = .002 and P = .03, respectively). No other factors were associated with survival after diagnosis of CSM. CONCLUSION AND CLINICAL IMPORTANCE: The skin or subcutaneous tissue can be the first osteosarcoma metastatic site detected. After CSM diagnosis, the prognosis is grave with median survival <2 months. Although this finding could have been biased by case selection, treatment with surgery and chemotherapy may improve outcome.

Retrospective evaluation of anemia and erythrocyte morphological anomalies in dogs with lymphoma or inflammatory bowel disease.

OBJECTIVE To assess the prevalences of anemia and various RBC anomalies in dogs with lymphoma versus inflammatory bowel disease (IBD) and to evaluate potential relationships between these variables and the severity of lymphoma. DESIGN Retrospective cross-sectional study. ANIMALS 82 client-owned dogs. PROCEDURES Medical records and blood smears were reviewed for dogs in which IBD or lymphoma had been diagnosed between January 1, 2006, and December 31, 2014, and for healthy dogs evaluated during that time frame. Hematologic data were analyzed, and results were compared among groups of healthy dogs, dogs with IBD, and dogs with lymphoma. Results were also compared within the lymphoma group between dogs further grouped on the basis of lymphoma clinical stage, substage, and cell size. RESULTS Prevalence of anemia was significantly higher in dogs with lymphoma (17/32 [53%]) than in dogs with IBD (5/23 [22%]). The total number of different RBC anomalies was significantly higher in dogs with lymphoma than in dogs that were healthy or had IBD. A cutoff of 3 different RBC anomalies/dog enabled differentiation between lymphoma and IBD, with a sensitivity and specificity of 71% and 70%, respectively (area under the fitted curve, 0.7239 ± 0.0727). The presence of eccentrocytes was the only individual RBC anomaly significantly more common in dogs with lymphoma (8/28 [29%]) versus dogs with IBD (1/23 [4%]). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that detection of anemia combined with ≥ 3 RBC morphological anomalies, particularly eccentrocytes, on blood smears should increase the clinical suspicion of lymphoma, compared with IBD, in dogs.

A case of canine high-grade T-cell lymphoma immunophenotypically consistent with T-zone lymphoma.

A 9-year-old spayed female Curly Coated Retriever was referred for evaluation of generalized peripheral lymphadenomegaly. The dog was clinically healthy on presentation with no anomalies detected on complete blood count, serum biochemistry, urinalysis, or three-view thoracic radiographs. Fine-needle aspiration (FNA) and cytology of the peripheral lymph nodes were consistent with lymphoma with an intermediate-sized lymphoid population. Flow cytometry of peripheral lymph nodes was consistent with a homogeneous population of CD4+ T cells that had lost expression of the pan-leukocyte antigen CD45. Variable expression of CD21, CD25, and class II major histocompatibility complex (MHC) were also noted. This was considered consistent with T-zone lymphoma (TZL), although the T cells were noted to be larger than usual based on flow cytometry. Due to the suspected indolent nature of this patient's disease and clinical progression, a careful monitoring approach was initially discussed with the owner. However, additional diagnostic testing was performed to confirm the diagnosis. Bone marrow cytology did not show any significant anomalies. The largest lymph node (left mandibular) was extirpated and submitted for histopathology. Based on the lymph node architecture, cellular features, and high mitotic activity, an unexpected diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) was made. The dog was started on CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. This case illustrates the limitations of using flow cytometry as the sole means of diagnosing TZL and highlights the importance of using complementary tests when subtyping canine lymphoma, which is significant when considering a patient's treatment plan and prognosis.