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. 2022 Sep 15;140(11):1229-1253.
doi: 10.1182/blood.2022015851.

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee

Elias Campo  1 , Elaine S Jaffe  2 , James R Cook  3 , Leticia Quintanilla-Martinez  4 , Steven H Swerdlow  5 , Kenneth C Anderson  6 , Pierre Brousset  7 , Lorenzo Cerroni  8 , Laurence de Leval  9 , Stefan Dirnhofer  10 , Ahmet Dogan  11 , Andrew L Feldman  12 , Falko Fend  4 , Jonathan W Friedberg  13 , Philippe Gaulard  14   15 , Paolo Ghia  16 , Steven M Horwitz  17 , Rebecca L King  12 , Gilles Salles  17 , Jesus San-Miguel  18 , John F Seymour  19 , Steven P Treon  6 , Julie M Vose  20 , Emanuele Zucca  21 , Ranjana Advani  22 , Stephen Ansell  23 , Wing-Yan Au  24 , Carlos Barrionuevo  25 , Leif Bergsagel  26 , Wing C Chan  27 , Jeffrey I Cohen  28 , Francesco d'Amore  29 , Andrew Davies  30 , Brunangelo Falini  31 , Irene M Ghobrial  6   32 , John R Goodlad  33 , John G Gribben  34 , Eric D Hsi  35 , Brad S Kahl  36 , Won-Seog Kim  37 , Shaji Kumar  23 , Ann S LaCasce  6 , Camille Laurent  7 , Georg Lenz  38 , John P Leonard  39 , Michael P Link  40 , Armando Lopez-Guillermo  41 , Maria Victoria Mateos  42 , Elizabeth Macintyre  43 , Ari M Melnick  44 , Franck Morschhauser  45 , Shigeo Nakamura  46 , Marina Narbaitz  47 , Astrid Pavlovsky  48 , Stefano A Pileri  49 , Miguel Piris  50 , Barbara Pro  51 , Vincent Rajkumar  12 , Steven T Rosen  52 , Birgitta Sander  53 , Laurie Sehn  54 , Margaret A Shipp  6 , Sonali M Smith  55 , Louis M Staudt  56 , Catherine Thieblemont  57   58 , Thomas Tousseyn  59 , Wyndham H Wilson  56 , Tadashi Yoshino  60 , Pier-Luigi Zinzani  61 , Martin Dreyling  62 , David W Scott  54 , Jane N Winter  63 , Andrew D Zelenetz  17   64
Affiliations

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee

Elias Campo et al. Blood. .

Erratum in

Abstract

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

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Figures

Figure 1.
Figure 1.
Suggested diagnostic studies in FL grade 3. Upper left: Cells from FL grade 3A are shown with hematoxylin and eosin (H&E) and Giemsa stains. Note the admixture of centrocytes and centroblasts (>15 per high power field) highlighted in the Giemsa stain. Upper right: Cells from FL grade 3B are shown with H&E and Giemsa stains. The follicles are composed of sheets of centroblasts with open chromatin, several nucleoli, and abundant basophilic cytoplasm highlighted with the Giemsa stain. Upper middle: Cells from FL with ambiguous morphology are shown. They are medium-size with open chromatin but inconspicuous nucleoli unlike centroblasts (arrows) and without the cytologic features of centrocytes. With ambiguous morphology (blue arrow), the presence of BCL2 rearrangement and/or CD10 expression favors the diagnosis of FL grade 3A; if both are absent, a diagnosis of FL grade 3B is favored. In patients who have FL grade 3B with IRF4/MUM1 expression, IRF4-FISH analysis is recommended to exclude the diagnosis of large B-cell lymphoma with IRF4 rearrangement. Original magnification ×400. BM, bone marrow.
Figure 2.
Figure 2.
Algorithm for the diagnostic workup of aggressive B-cell lymphomas. The current algorithm for diagnosing aggressive large B-cell lymphomas starts with a biopsy collection from a lymph node (excision or needle biopsy) or a biopsy of an extranodal site. The diagnosis of the different lymphoma entities is based on a combination of morphology, immunophenotype, EBER in situ hybridization, FISH analysis, and B-cell clonality analysis. Advances in the understanding of DLBCL herald a transition to a molecular genetic classification (red arrow). This genetic classification is based on mutational profile, somatic copy number alterations, and structural variants. The depicted molecular subtypes were identified in 3 different studies indicating that these subgroups reflect true biological differences. On the basis of these molecular studies, a predictor model was developed that dissects the cell-of-origin and stratifies further the molecular classification into 7 genetic subtypes with apparently clinical relevance. The acronyms indicate the names given in the different studies to the same identified biological group.
Figure 3.
Figure 3.
Large B-cell lymphoma with 11q aberration. (A) Low power view of large-cell morphology, abundant mitoses, and the characteristic starry-sky pattern with abundant macrophages with coarse apoptotic bodies (original magnification ×200; H&E stain). (B) Higher magnification reveals the large centroblastic morphology of the tumor cells (original magnification ×400; H&E stain). Inset: FISH analysis demonstrated the typical 11q alterations (blue, centromere; red, 11q24 loss; green, 11q23 gain; ×1000). The cytology of the cells might be medium-size to large-size cells. The morphology and mutational profile justify the change in the name of this entity (previously, Burkitt-like lymphoma with 11q aberration).
Figure 4.
Figure 4.
Morphologic characterization of highly proliferative B-cell lymphomas. (A-B) This DLBCL, NOS has many mitotic figures, but many of the neoplastic cells are typical large transformed cells that do not resemble either BL cells or B lymphoblasts. Chromosomal analysis showed a complex karyotype, but there was no evidence of MYC or BCL2 rearrangement. (C-D) This HGBCL, NOS is composed of relatively small blastoid-appearing cells with many mitotic figures, reminiscent of a B-lymphoblastic leukemia/lymphoma. TdT was negative. It had a complex karyotype that included t(14;18)(q32;q21) and i(17)(q10). (E-F) This HGBCL with MYC and BCL6 rearrangements (without evidence of IGH::BCL2) resembles BL with intermediate-size transformed cells and a starry-sky appearance with scattered tingible body macrophages. The cytospin (inset) demonstrated cytoplasmic vacuoles. Unlike classic BL, it was BCL2 protein positive and had only equivocal CD10 positivity. All panels were stained with H&E except for the inset stained with Wright-Giemsa stain. Original magnification ×400 for panels A, C, and E; original magnification ×1000 for panels B, D, and F and inset.
Figure 5.
Figure 5.
Algorithm for the classification workup of nodal PTCLs. The current algorithm for diagnosing PTCL requires immunophenotypic study with a panel of markers that, together with viral analysis (HTLV1, EBV), will orient the pathologist to consider and diagnose specific entities. In ambiguous cases, sequencing studies may help diagnose some entities, particularly follicular helper T-cell lymphoma. PTCL, NOS is established when other specific entities are excluded. Phenotypic analysis or analysis by GEP may subdivide patients with PTCL, NOS, but this subclassification is not routinely incorporated into clinical diagnosis and requires further studies for clinical validation. ATLL, adult T-cell leukemia/lymphoma; GrB, granzyme B; Per, perforine.
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