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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 1011-1019
The Molecular and Phenotypic Profile of Primary Central Nervous
System Lymphoma Identifies Distinct Categories of the Disease and Is
Consistent With Histogenetic Derivation From Germinal
Center-Related B Cells
Luigi Maria Larocca,
Daniela Capello,
Alessandro Rinelli,
Simonetta Nori,
Andrea Antinori,
Annunziata Gloghini,
Antonella Cingolani,
Anna Migliazza,
Giuseppe Saglio,
Sophie Cammilleri-Broet,
Martine Raphael,
Antonino Carbone, and
Gianluca Gaidano
From the Institute of Pathology, Catholic University of the Sacred
Heart, Rome; Division of Internal Medicine, Department of Medical
Sciences, University of Torino at Novara, Novara; Institute of
Infectious Diseases, Catholic University of the Sacred Heart, Rome;
Division of Pathology, INRCCS-Centro di Riferimento Oncologico, Aviano;
Department of Clinical and Biological Sciences, University of Torino,
Orbassano-Torino, Italy; Division of Oncology, Department of Pathology,
College of Physicians & Surgeons, Columbia University, New York, NY;
Laboratoire de Neuropathologie, Pitié Salpètrière,
Paris; Service d'Hematologie Biologique, Hopital Avicenne, Bobigny,
Universitè de Paris XIII, Paris, France.
Primary central nervous system lymphoma (PCNSL) is a major cause of
morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals. The precise histogenetic derivation and the
molecular pathogenesis of PCNSL is poorly understood. In an attempt to
clarify the histogenesis and pathogenesis of these lymphomas, 49 PCNSL
(26 acquired immunodeficiency syndrome [AIDS]-related and 23 AIDS-unrelated) were analyzed for multiple biologic markers, which are
known to bear histogenetic and pathogenetic significance for mature
B-cell neoplasms. PCNSL associated frequently (50.0%) with mutations
of BCL-6 5 noncoding regions, which are regarded as a
marker of B-cell transition through the germinal center (GC).
Expression of BCL-6 protein, which is restricted to GC B cells
throughout physiologic B-cell maturation, was detected in 100%
AIDS-unrelated PCNSL and in 56.2% AIDS-related cases. Notably, among
AIDS-related PCNSL, expression of BCL-6 was mutually exclusive with
expression of Epstein-Barr virus (EBV)-encoded latent
membrane protein (LMP)-1 and, with few exceptions, also of BCL-2. All
but one PCNSL expressed hMSH2, which among mature B cells selectively
stains GC B cells. These data suggest that PCNSL may be frequently
related to GC B cells and may be segregated into two major biologic
categories based on the expression pattern of BCL-6, LMP-1, and BCL-2.
BCL-6+/LMP-1 /BCL-2 PCNSL
occur both in the presence and in the absence of HIV infection and
consistently display a large noncleaved cell morphology. Conversely, BCL-6/LMP-1+/BCL-2+ PCNSL
are restricted to HIV-infected hosts and are represented by lymphomas
with immunoblastic features. These data are relevant for the
pathogenesis and histogenesis of PCNSL and may be helpful to segregate
distinct biologic and prognostic categories of these lymphomas.
© 1998 by The American Society of Hematology.
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