The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

Abstract

We herein present an overview of the upcoming 5^th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4^th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5^th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

Fig. 1. Summary of the relationship between splenic B-cell lymphoma entities as named and defined in the revised 4^th edition of the WHO classification (WHO-HAEM4R) and in the present 5^th edition (WHO-HAEM5).

Some cases previously classified as B-prolymphocytic leukaemia do represent (blastoid) mantle cell lymphoma (as was already indicated in WHO-HAEM4R) or prolymphocytic progression of CLL. Cases classified in WHO-HAEM4R as CLL/SLL with ≥ 15% of prolymphocytes are now classified as prolymphocytic progression of CLL, cases with <15% of prolymphocytes remain CLL/SLL in WHO-HAEM5. Remaining cases are now renamed as “splenic B-cell lymphoma/leukaemia with prominent nucleoli” (SBLPN). This latter entity has absorbed cases formerly classified as hairy cell leukaemia variant (HCLv) and very rare cases of splenic marginal zone lymphoma with similar morphological features. It should be noted that the distinction between the various entities cannot always be made in the absence of a splenectomy specimen.

Fig. 2. Aetiology and recurrent genetic abnormalities in extranodal marginal zone lymphoma (EMZL) of various sites.

An important clinical application is that BIRC3::MALT1 identifies those cases of the gastric EMZL not responding to H. pylori eradication. As many of the genes involved in EMZL have not been uniformly investigated across different sites, only the recurrent genetic changes fundamental to the understanding of EMZL pathogenesis are presented. The height of the boxes under sites does not reflect the frequencies of these lymphomas. trans translocation, mut mutation, del: deletion.

Fig. 3. Summary of the relationship between large B-cell lymphoma (LBCL) entities as named and defined in the revised 4^th edition of the WHO classification (WHO-HAEM4R) and in the present 5^th edition (WHO-HAEM5).

* “Rare B-cell lymphomas” refer to those fulfilling definitions of specific clinico-pathological entities while incidentally bearing concomitant MYC and BCL2 rearrangements. Examples are fluid-overload-associated large B-cell lymphomas and rare follicular lymphomas. R rearrangement, G germline configuration.

Fig. 4. Algorithm for classification of aggressive B-cell lymphomas in WHO-HAEM5 in the light of MYC, BCL2 and BCL6 rearrangement and complex 11q gain/loss patterns.

HGBL high grade B-cell lymphoma, R rearrangement, G germline configuration.

Fig. 5. Summary of the relationship between immunodeficiency-associated lymphoid proliferations and lymphomas as named and defined in the revised 4^th edition of the WHO Classification (WHO-HAEM4R) and in the present 5^th edition (WHO-HAEM5).

The overarching concept applied in WHO-HAEM5 recognizes the pathological and biological similarities between proliferations presenting in various immune deficiency settings, while acknowledging their specific features. Outside the shared entities, unique proliferations are especially typical for various inborn errors of immunity (IEI). EBVMCU: EBV-positive mucocutaneous ulcer.

Fig. 6. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach.

The gastric mucosa shows expansion of the lamina propria by an atypical lymphoid infiltrate. The tumour cells are medium-sized, often with pale-staining cytoplasm.

Fig. 7. Nodal TFH-cell lymphoma (nTFHL).

A Nodal TFH-cell lymphoma, angioimmunoblastic-type (nTFHL-AI). The normal architecture of the lymph node is effaced. There is a diffuse infiltrate of medium-sized, slightly atypical lymphocytes, sometimes with clear cytoplasm. One of the hallmarks of the disease is the proliferation of arborizing post-capillary vessels consistent with high endothelial venules. B Nodal TFH-cell lymphoma, follicular-type (nTFHL-F). In this example, progressive transformation of germinal centre-like nTFHL-F, clusters of atypical lymphoid cells with pale cytoplasm are embedded in a background of small lymphocytes of mantle zone type. The inset shows strong expression of PD1 in the tumour cells. C Nodal TFH-cell lymphoma, not otherwise specified. This tumour is composed of a sheet-like proliferation of medium-sized to large neoplastic cells.

Fig. 8. Nodal EBV-positive T- and NK-cell lymphoma.

This lymphoma shows a diffuse infiltrate of relatively monotonous, medium-sized to large cells, sometimes reminiscent of centroblasts. Inset: in-situ hybridization for EBERs identifies EBV infection in virtually all tumour cells.