How Many Ontogenetic Roads to Mantle-Cell Lymphoma? Immunogenetic and Immunohistochemical Evidence

Autor: Richard Rosenquist, Elias Campo, Andreas Agathangelidis, Christer Sundström, Evangelia Stalika, Anastasia Hadzidimitriou, Kostas Stamatopoulos, Evi Pouliou, Achilles Anagnostopoulos, Penelope Korkolopoulou, Paolo Ghia, Theodora Papadaki, Maurilio Ponzoni, Kypros Dimosthenous, Aliki Xochelli, Efstratios Patsouris, Alba Navarro, Lesley-Ann Sutton, George Kanellis, Birgitta Sander
Rok vydání: 2014
Předmět:
Zdroj: Blood. 124:3005-3005
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v124.21.3005.3005
Popis: Until quite recently, the prevailing view, adopted by the WHO 2008 Classification, was that mantle-cell lymphoma (MCL) originates from a peripheral B cell located within the inner mantle zone, an area comprised of naïve pre-germinal center (GC) type B cells. However, this notion has been challenged by molecular and functional evidence. Indeed, MCL is characterized by a skewed repertoire of immunoglobulin heavy variable (IGHV) genes and by some imprint of somatic hypermutation (SHM) in the clonotypic IGHV genes of the great majority (~70%) of cases, indicating antigen selection. Furthermore, both relapsed/refractory and treatment-naïve patients with MCL exhibit remarkable responses to B-cell receptor signaling inhibitors, strongly supporting a role for microenvironmental triggering in the natural history of MCL. In the present study, we sought to obtain additional insight into MCL ontogeny through a combined morphologic, immunohistochemical and immunogenetic analysis of 230 patients with a diagnosis of MCL according to the 2008 WHO Classification criteria. The study group included 139 nodal, 32 extranodal, 18 primary splenic MCLs as well as 41 bone marrow biopsies (BMB) infiltrated by MCL. Morphologically, 144/206 (70%) cases were ascribed to the common variety, while 48/206 (23.3%) and 14/206 (6.7%) were characterized as blastoid or pleomorphic variant, respectively. The immunohistochemical analysis (on paraffin sections) focused on CD27, DBA.44 and IRF4 (MUM1), markers not normally expressed by the naïve pre-germinal centre B-cell of the inner mantle zone. The results were as follows: (i) 117/214 (54.7%) cases positive for CD27 expression; (ii) 18/176 (10.2%) cases positive for DBA.44; (iii) 53/98 (54%) cases positive for IRF4. Amongst CD27+ cases, 10/86 (11.6%) were also positive for DBA.44, whereas 27/51 (52.9%) were also positive for IRF4. Immunogenetic information regarding IGHV-IGHD-IGHJ gene rearrangements was available for 167 cases of the study. Fifty of 167 cases (30%) carried IGHV genes with no SHM (100% identity to the germline, GI), whereas the remaining 117 cases (70%) bore some imprint of SHM: in particular, 95/167 cases (56.8%) carried IGHV genes with 97-99.9% GI, while 22/167 cases (13.2%) carried IGHV genes with Disclosures Stamatopoulos: Janssen Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Databáze: OpenAIRE
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