Intravascular large B-cell lymphoma: report of three cases and analysis of the mTOR pathway

Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive and often fatal non-Hodgkin lymphoma characterized by preferential growth of malignant B-cells within the lumina of small vessels. Rituximab plus anthracycline-based chemotherapy is the current standard regimen for IVLBCL, however it has minimal efficacy in relapsed or refractory diseases. Recent clinical trials have shown a significant anti-lymphoma activity of mammalian target of rapamycin (mTOR) inhibitors in relapsed and refractory diffuse large B-cell lymphoma (DLBCL); however, the activation status of the mTOR pathway and the therapeutic potential of mTOR inhibitors in IVLBCL have not yet been studied. Here we described the clinicopathological features of 3 cases of IVLBCL diagnosed at our institutions, and evaluated the activation status of the mTOR signaling in these tumors. Our results showed that the mTOR complex 2 pathway was selectively upregulated in IVLBCL, as evidenced by a predominant nuclear localization of the activated form of mTOR (p-mTOR at Ser2448) with concomitant overexpression of nuclear p-Akt (Ser473) and vascular endothelial growth factor (VEGF)-A in the lymphoma cells. These data suggest that overactivation of mTOR pathway may play a role in lymphomagenesis of IVLBCL and mTORC2 inhibitors may be beneficial in treating IVLBCL.