Primary adrenal lymphoma causing hypoaldosteronism in a cat.

CASE SUMMARY: A 10-year-old, 5.1 kg (11.2 lb), male castrated cat was presented with signs of lethargy and decreased appetite at home after being previously healthy. Serum biochemical analysis identified normokalemia (5.1 mmol/l; reference interval [RI] 3.4-5.6 mmol/l) and severe hyponatremia (123 mmol/l; RI 145-158 mmol/l), with an Na/K ratio of 24 (RI 32-41). Baseline serum cortisol was low to normal, but serum aldosterone was markedly decreased with a pre-adrenocorticotropic hormone stimulation concentration of 13 pmol/l (RI 194-388 pmol/l) and post-adrenocorticotropic hormone stimulation concentration of 21 pmol/l (RI 277-721 pmol/l). Hematologic and biochemical analyses were otherwise unremarkable. Abdominal ultrasound revealed bilaterally enlarged adrenal glands with no other abnormalities noted; thoracic radiographs also did not identify any signs of metastasis. Fine-needle aspiration was strongly suggestive of lymphoma of the adrenal glands, and PCR for antigen receptor rearrangement was positive for B-cell clonal expansion; based on these findings, a diagnosis of primary adrenal B-cell lymphoma was made. Stable disease was achieved for a short period of time following vincristine, cyclophosphamide, prednisolone and fludrocortisone therapy, followed by progressive adrenal enlargement and electrolyte derangements that responded to neither doxorubicin nor adjustments in fludrocortisone dosage. Ultrasonographic metastasis was not identified at any time, and other organ derangements were not noted on hematologic or biochemical analyses. The cat was euthanized 55 days after initial presentation. RELEVANCE AND NOVEL INFORMATION: This is the first report of primary adrenal lymphoma in a cat, with presenting signs compatible with hypoaldosteronism. Lymphoma should be a differential for cats presenting with adrenal enlargement or clinical signs and biochemical changes consistent with hypoaldosteronism or hypoadrenocorticism.

MHC-dependent desensitization of intrinsic anti-self reactivity.

The survival of naive T cells is compromised in the absence of molecules encoded by the major histocompatibility complex (MHC) while antigen-experienced T cells survive. We hypothesized that survival pressures in an in vivo, MHC-deficient environment would permit enrichment of less frequent antigen-experienced autoreactive cells at the expense of the majority of antigen naive T cells. To test this hypothesis, we generated MHC class I- and class II-deficient mice in NOD and C57Bl/6 (B6) backgrounds, and examined the capacity of adoptively transferred autoimmune-prone NOD T cells, or non-autoimmune prone naive B6 T cells, respectively, to reject transplanted wild-type pancreatic islets or transplantable tumors in the MHC-deficient mice. In the MHC-deficient environment, CD4 T cells acquired self-hostile properties (islet rejection and tumor invasion) that were independent from their genetic propensity for autoreactivity, while CD8 T cells required appropriate prior exposure to antigen in order to survive and function (reject tumor) in this environment; however, disengagement of Tob1, a negative regulator of proliferation, led to a reverse phenotype with regard to persistence of CD4 and CD8 T cells in the MHC-deficient environment. Our data suggest that self-peptide/MHC interactions have dual roles to facilitate survival and restrain autoreactivity, thus acting as integral components of an intrinsic network of negative regulation that maintains tolerance.

Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation.

OBJECTIVE: Two competing hypotheses can be formulated regarding the origin of canine hemangiosarcoma (HSA). One states HSA originates from differentiated vascular endothelial cells that undergo mutations which endow them with malignant potential. The other states HSA originates from transformed hemangioblastic stem cells. This study was designed to begin to distinguish between these possibilities, as well as to test if flow cytometry was sufficiently sensitive to detect malignant cells in blood samples from dogs with HSA. METHODS: We used multiparameter flow cytometry to examine expression of cell-surface determinants associated with hematopoietic precursors (c-kit, CD34, CD133, CD45) or with lineage-committed cells (CD3, CD11b, CD14, CD21, CD105, CD146, alphavbeta3-integrin) in HSA cell lines and in blood samples from healthy dogs or dogs with HSA. RESULTS: The data show that HSA cells coexpress surface markers associated with hematopoietic precursors and with commitment to endothelial lineage, providing a means to identify their presence in circulation and distinguish them from normal or malignant white blood cells. The percentage of cells that coexpressed these markers ranged from 0.5 to 1.25% for HSA dogs, and was less than 0.3% for unaffected dogs or dogs with HSA that had the tumors removed within 48 hours prior to obtaining samples. CONCLUSIONS: The results place the ontogeny of HSA with multipotential bone marrow-derived stem cells whose progeny arrest differentiation at the hemangioblast or angioblast stage. In addition, these expression patterns may assist to confirm an HSA diagnosis, monitor minimal residual disease, and detect the disease in early stages.