Large cell non Hodgkin’s lymphoma: what is new in the WHO classification?

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non Hodgkin lymphoma (NHL), representing 35- 40% of cases. It is a neoplasm constituted of large B lymphoid cells with nuclear size equal to or exceeding normal macrophage nuclei or more than twice the size of a normal lymphocyte, that has a diffuse growth pattern. Morphological, biological and clinical studies have subdivided diffuse large B-cell lymphomas into morphological variants, molecular and immunophenotypical subgroups and distinct disease entities, which are now quoted in the IV edition of the WHO Classification of Tumours of the Haemopoietic and Lymphoid Tissues (see Table 1). However, a large number of cases remain that may be biologically heterogeneous, and there are no clear and accepted criteria for their further subdivision. These are classified as DLBCL, not otherwise specified (NOS). Importantly, recent gene expression profile (GEP) studies demonstrated that such cases can present with different features, possibly related to a different histogenesis, with relevant prognostic impact. Noteworthy, surrogate markers of GEP can be routinely applied to diagnostic material by immunohistochemistry, being possibly useful for patients’ stratification and therapeutic decision.1-4