B-Cell Lymphomas, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
Cet article présente une mise à jour des recommandations du "National Comprehensive Cancer Network" concernant la prise en charge d'un lymphome à cellules du manteau, un sous-type hétérogène de lymphome à cellules B
Mantle cell lymphoma (MCL) comprises approximately 4% of all newly diagnosed non-Hodgkin lymphomas (NHL).1 MCL is a heterogenous subtype of B-cell NHL, thought to exhibit the unfavorable characteristics of both indolent and aggressive NHL owing to the incurability of disease with conventional chemoimmunotherapy and a typically more aggressive disease course compared with indolent NHL.2
MCL is a CD5-positive small B-cell lymphoma typically characterized by the reciprocal chromosomal translocation t(11;14), juxtaposing the CCND1 gene with the IGH locus, resulting in the overexpression of cyclin D1; the diagnosis of MCL generally requires the expression of cyclin D1.3
Cyclin D1-negative MCL with otherwise typical immunophenotype has also been reported, although rare (<5%).4,5 Rearrangements involving the CCND2 gene are present in 55% of cyclin D1-negative MCL and are associated with high expression of cyclin D2 mRNA and/or protein.6 Gene expression profiling (GEP) and microRNA (miRNA) profiling showed that the genomic signatures of cyclin D1-negative MCL were similar to those of cyclin D1-positive MCL.5–7 The pathologic features and clinical characteristics of cyclin D1-negative MCL appear to be similar to those of cyclin D1-positive MCL.6,7 Thus, in the absence of data suggesting otherwise, cyclin D1-negative MCL should not be managed differently than cyclin D1-positive MCL.
The updated WHO Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification (ICC) reflect the heterogeneity of this entity and recognize the 3 subtypes of MCL with distinct clinicopathologic and molecular features: classic MCL (nodal or extranodal), leukemic and non-nodal MCL, and in situ mantle cell neoplasia (ISMCN).8,9
Classic MCL is typically SOX11- and cyclin D1-positive and IGHV unmutated with a generally aggressive clinical course.10 The blastoid/pleomorphic variant is characterized by different cytologic features resembling lymphoblasts or large cell lymphomas, a more aggressive clinical course, and is often associated with poor prognostic features such as TP53 mutations and high Ki-67 proliferation index.10,11
The leukemic and non-nodal subtype typically is SOX11-negative, IGHV-mutated, and has an indolent disease course. This variant most commonly presents with peripheral blood, bone marrow, and splenic involvement, as well as low tumor burden and a Ki-67 proliferation index <10%.10,12,13 However, there are some presentations with gastrointestinal (GI) involvement.
ISMCN is characterized by the preservation of the lymph node architecture and cyclin D1-positive B cells that are restricted to the mantle zones with minimal expansion of the mantle zone (and with only minimal or no spread of cyclin D1-positive cells in the interfollicular area).14,15 ISCMN has also been identified in reactive lymph nodes from patients without a history of lymphoma and while some patients with ISMCN may have or develop MCL, most patients do not.15,16 Nonetheless, a thorough systemic evaluation (eg, biopsy, peripheral blood flow cytometry, physical examination, and imaging studies) is recommended to distinguish ISMCN from overt MCL with a mantle zone pattern.15,16
Journal of the National Comprehensive Cancer Network , article en libre accès, 2026