Grey-Zone lymphomas: the fear of all lymphoma pathologists

Abstract

Grey-zone lymphomas (GZLs) are operationally defined as lymphomas that show morphologic, immunophenotypic and frequently genetic overlap between two well-defined and accepted lymphoid entities. In 2008, the WHO defined two provisional categories, including mediastinal grey-zone lymphomas (MGZL) [biopsies showing overlapping features between primary mediastinal large cell lymphoma (PMBCL) and nodular sclerosis Hodgkin lymphoma (NSHL)] and cases that lie between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). A third grey-zone also exists between cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and so-called T cell/ histiocyte-rich large B cell lymphoma (TCHRBCL). MGZLs are typically of two major types: one that resembles NSHL but shows a B cell phenotype, and cases that are PMBCL-like but reveal overlapping phenotypic features with Hodgkin lymphoma. Both clinical features and survival distinguish these cases from both PMBCL and NSHL. The GZLs between DLBCL and BL are more frequent and pose a diagnostic challenge. They are less well defined, but show an enrichment of cases harbouring MYC translocations with BCL2 and/or BCL6 rearrangements. Distinguishing these cases from de novo DLBCL has clinical relevance. Lastly, the GZ between TCHRBCL and NLPHL will be discussed using illustrative cases.