Cerebral intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which neoplastic lymphocytes proliferate within the lumina of small blood vessels in the absence of a primary extravascular mass or leukemia. IVL is described in humans, dogs, one cat and one horse. The clinical symptoms of the disease are dependent on the specific organ involvement, which most often includes the central nervous system (CNS) and skin. The aim of our study was to characterize the clinical and neuropathological features of 10 cases of canine IVL restricted to the CNS. The study included 6 females and 4 males with an average age of 8 years (range 2.5 to 13 years). Immunohistochemistry (IHC) using anti-CD3 and anti-CD20 antibodies was performed to typify the neoplastic lymphocytes. Anti-CD44 and anti-CD29 antibodies were used to investigate the pathogenetic mechanism leading to the intravascular aggregation of the neoplastic lymphocytes, since CD44 and CD29 are molecules known to be involved in lymphocyte and endothelial adhesion phenomena. The same IHC panel was also applied on 8 cases of primary and metastatic canine CNS lymphoma in order to compare IVL immunoreactivity. The main clinical signs shown by dogs with cerebral IVL were depression, seizures and gait deficits. Magnetic resonance imaging showed several areas of hyperintensity distributed mainly in the forebrain with almost no significant enhancement post intravenous gadolinium administration. Grossly, lesions were found in 6 cases and included focal extensive or multiple hemorrhagic areas. Microscopic examination revealed numerous veins and capillaries filled with neoplastic lymphoid cells, involving both neuroparenchymal and meningeal vessels, and accompanied by various degrees of edema, hemorrhage and thrombosis. Three IVLs were typified as T-cell (CD3+), 3 as B-cell (CD20+) and 4 as non-B non-T (CD3-, CD20-). Regarding primary and metastatic canine CNS lymphomas, 4 were classified as T-cell, 3 as B-cell, and one as non-B non-T. In IVLs, neoplastic lymphocytes showed marked expression of CD44, whereas in primary and metastatic lymphomas CD44 positive cells were detected only in 2 cases. CD29 immunolabeled cells were observed in 4 IVLs and in one primary CNS lymphoma. In human IVL, CD44 is invariably expressed on the cytoplasmic membrane of neoplastic cells, presumably predisposing to the formation of lymphocytes aggregates. Moreover, the transvascular lymphocyte migration could be impaired because of lack of CD29 expression on neoplastic cells, limiting their proliferation within the intravascular compartment. CD44 immunoreactivity in canine IVL was consistent with the findings reported in human IVL, whereas CD29 was inconsistently immunonegative, confirming only partially the pathogenetic mechanism suggested for the human counterpart.