Large B-Cell Lymphomas in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms-Updated Classification and New Concepts

Abstract

The family/class of the large B-cell lymphomas (LBCL) in the 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumors (WHO-HAEM5) features only a few major changes as compared to the 4th edition. In most entities, there are only subtle changes, many of them only representing some minor modifications in diagnostic terms. Major changes have been made in the diffuse large B-cell lymphomas (DLBCL)/high-grade B-cell lymphomas (HGBL) associated with MYC and BCL2 and/or BCL6 rearrangements. This category now consists of MYC and BCL2 rearranged cases exclusively, while the MYC/BCL6 double hit lymphomas now constitute genetic subtypes of DLBCL, not otherwise specified (NOS) or of HGBL, NOS. Other major changes are the conceptual merger of lymphomas arising in immune-privileged sites and the description of LBCL arising in the setting of immune dysregulation/deficiency. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of the different entities are provided.

Keywords: WHO-HAEM5; classification; diffuse large B-cell lymphoma; genetics; large B-cell lymphoma.

Figure 1

Diffuse large B-cell lymphoma, NOS (H&E ×400). There is a diffuse effacement of the architecture by medium-sized and large blastic cells that have a moderately basophilic cytoplasm and round nuclei with light chromatin and one to several nucleoli.

Figure 2

Schematic presentation of maturating and differentiating pathways in germinal centers including some biological characteristics of GCB-like and ABC-like lymphomas derived from different compartments of the GC. The lower panel shows the more recently proposed algorithms in the molecular subclassification of DLBCL including their main defining genes.

Figure 3

Diffuse large B-cell-lymphoma/High-grade-B-cell-lymphoma with MYC and BCL2 rearrangements (H&E ×400). This tumor has a DLBCL morphology. Upon FISH, it showed a “triple hit” constellation with MYC, BCL2, and BCL6 rearrangements.

Figure 4

Algorithm for the classification of aggressive B-cell lymphomas in WHO-HAEM5 according to rearrangements of MYC, BCL2, and BCL6 and/or presence of the complex 11q gain/loss patterns.

Figure 5

High-grade B-cell lymphoma with 11q aberrations (H&E ×400). These tumors as a rule are composed of medium-sized blastic cells reminiscent of, but more pleomorphic than, those of Burkitt lymphoma. Note the starry sky pattern with coarse cellular debris in the macrophages.

Figure 6

Lymphomatoid granulomatosis. (A) (H&E ×200). There is an angiocentric infiltration of several medium-sized blood vessels by a polymorphic lymphomatous infiltrate. (B) (×400) LMP staining confirms EBV association and highlights medium-sized to large blasts infected by EBV.

Figure 7

EBV-positive diffuse large B-cell lymphoma (H&E ×400). This lymphoid tumor shows numerous anaplastic Hodgkin- and Reed–Sternberg-like cells. Upon EBER in situ hybridization, practically all nuclei were positive. On the upper left, an area of necrosis is seen.

Figure 8

Fibrin-associated large B-cell lymphoma (A) (H&E ×200). Large transformed cells are floating in the background of fibrin and cellular debris. (B) (×200) EBER in situ hybridization confirmed EBV association.

Figure 8

Fibrin-associated large B-cell lymphoma (A) (H&E ×200). Large transformed cells are floating in the background of fibrin and cellular debris. (B) (×200) EBER in situ hybridization confirmed EBV association.

Figure 9

Fluid overload-associated large B-cell lymphoma (H&E ×200) This cytoblock preparation demonstrates massive shedding of large lymphoid cells into the pleural fluid.

Figure 10

Plasmablastic lymphoma (Giemsa ×400). This photomicrograph shows cohesively arranged immunoblastic/plasmablastic cells with broad deeply basophilic cytoplasm. In this case, CD20 was negative, and both CD138 and MUM1 were strongly expressed.

Figure 11

Primary large B-cell lymphomas (LBCL) of immune-privileged sites (H&E ×200). This is an example of a primary central nervous system LBCL with diffuse and perivascular infiltration patterns.

Figure 12

Primary cutaneous diffuse large B-cell lymphoma, leg type (H&E ×200). The large blastic tumor cells are invading the skin and reach the overlying epidermis.

Figure 13

Intravascular large B-cell lymphoma (H&E ×200). The typical blastic tumor cells are seen within distended capillary vessels of the leptomeninx.

Figure 14

(H&E ×100). In this example, large tumor cells, many of them with a clear cytoplasm, are seen in a background of in part compartmentalizing sclerosis.

Figure 15

High-grade B-cell lymphoma, NOS (H&E ×400). The tumor cells are small to medium-sized with scant cytoplasm and roundish nuclei. No apparent starry-sky pattern is seen. This tumor was negative for MYC, BCL2, and BCL6 rearrangements and also negative for 11q aberrations.