We herein present an overview of the upcoming 5^thedition 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^thedition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5^thedition 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.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a common low grade B-cell lymphoma arising from a background of chronic inflammatory disease at a number of mucosal sites. Those originating in the stomach are causatively linked to Helicobacter pylori infection and eradication of the bacterium with antibiotics leads to long-term complete regression of the lymphoma in ~70% of cases. Now, there is further evidence of linking Campylobacter jejuni, Borrelia burgdorferi and Chlamydia psittaci infection with immunoproliferative small intestine disease, MALT lymphoma of the skin and ocular adnexa respectively. t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, t(14;18)/IGH-MALT1 and t(3;14)/IGH-FOXP1 occur at considerably variable incidences in MALT lymphomas of different sites. The first three chromosome translocations are specifically associated with the MALT lymphoma entity and the oncogenic products of these translocations have been shown to target a common molecular pathway, i.e. the nuclear factor-κB pathway. Here, I review the recent advances in our understanding of the association of microbial pathogens with MALT lymphoma of various sites and the molecular genetics underlying the lymphoma development. [J Clin Exp Hematopathol 47(2) : 31-42, 2007]

Using a Burkitt lymphoma-like gene expression signature, we recently defined a high-risk molecular high-grade (MHG) group mainly within germinal centre B-cell like diffuse large B-cell lymphomas (GCB-DLBCL), which was enriched for MYC/BCL2 double-hit (MYC/BCL2-DH). The genetic basis underlying MHG-DLBCL and their aggressive clinical behaviour remain unknown. We investigated 697 cases of DLBCL, particularly those with MYC/BCL2-DH (n = 62) by targeted sequencing and gene expression profiling. We showed that DLBCL with MYC/BCL2-DH, and those with BCL2 translocation, harbour the characteristic mutation signatures that are associated with follicular lymphoma and its high-grade transformation. We identified frequent MYC hotspot mutations that affect the phosphorylation site (T58) and its adjacent amino acids, which are important for MYC protein degradation. These MYC mutations were seen in a subset of cases with MYC translocation, but predominantly in those of MHG. The mutations were more frequent in double-hit lymphomas with IG as the MYC translocation partner, and were associated with higher MYC protein expression and poor patient survival. DLBCL with MYC/BCL2-DH and those with BCL2 translocation alone are most likely derived from follicular lymphoma or its precursor lesion, and acquisition of MYC pathogenic mutations may augment MYC function, resulting in aggressive clinical behaviour.