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Int J Clin Exp Pathol 2011;4(8):782-790

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

Qi Shen, Xiuzhen Duan, Wei Feng, Nghia Nguyen, Angelo Lapus, Robert E. Brown, Lei Chen

Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, Houston, TX; Department of Pathology,
Loyola University Medical Center, Maywood, IL; Department of Pathology, North Cypress Medical Center, Cypress, TX; Department of Pathology,
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Received October 25, 2011; accepted November 3, 2011; Epub November 3, 2011; published November 30, 2011

Abstract: 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.

Keywords: Intravascular large B-cell lymphoma, mTOR, Akt, VEGF

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Address all correspondence to:
Lei Chen, MD
Department of Pathology & Laboratory Medicine
The University of Texas Medical School at Houston
6431 Fannin Street, MSB 2.136
Houston, TX, 77030, USA.
Tel: (713) 566-4690
Fax: (713) 566-5285
E-mail: Lei.Chen.1@uth.tmc.edu