Date Published: April 3, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Sylvia Hoeller, Christiane Copie-Bergman.
The current classification of lymphoid neoplasms is based on clinical information, morphology, immunophenotype, and molecular genetic characteristics. Despite technical and scientific progress, some aggressive B-cell lymphomas with features overlapping between two different types of lymphomas remain difficult to classify. The updated 2008 World Health Organization (WHO) classification of Tumours of the Hematopoietic and Lymphoid Tissues has addressed this problem by creation of two new provisional categories of B-cell lymphomas, unclassifiable; one with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and the second with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. We review here the diagnostic criteria of these two provisional entities and discuss new scientific findings in light of the 2008 WHO classification.
The current classification of lymphoid neoplasms is based on clinical information morphology, immunophenotype, and molecular genetic characteristics. Most lymphomas can be accurately classified. However, some lymphomas present with features transitional between diffuse large B-cell lymphomas (DLBCLs) and classical Hodgkin lymphoma (cHL) or DLBCL and Burkitt lymphoma (BL), and these are difficult to classify . These lymphomas have been reported in the literature using different terms, such as borderline lymphomas, B-cell lymphomas unclassifiable, atypical Burkitt lymphoma, Burkitt-like lymphomas, or gray zone lymphomas. The term “Gray Zone Lymphoma” was firstly used in 1998 at the “Workshop on Hodgkin’s disease and related diseases” to designate lymphomas at the border of cHL and other entities . This term was then further extended to lymphomas with overlapping features between BL and DLBCL. The 2008 updated WHO classification of Tumours of the Hematopoietic and Lymphoid Tissues proposed to assign these gray zone lymphomas to provisional categories called B-cell lymphomas unclassifiable with features intermediate between DLBCL and cHL (BCLu-DLBCL/cHL) and B-cell lymphomas unclassifiable with features intermediate between DLBCL and BL (BCLu-DLBCL/BL) . The reason to create these provisional categories is to enable to collect for further studies and to maintain the “purity” of well-defined categories. This would be particularly relevant for conducting clinical studies. This paper focuses on these two provisional entities introduced in the 2008 WHO classification of Tumours of the Hematopoietic and Lymphoid Tissues.
Primary mediastinal diffuse large B-cell lymphoma (PMBCL) and classical Hodgkin lymphoma of nodular sclerosing subtype (cHL-NS) have clinical, histopathological, and molecular similarities (Table 1). Both lymphomas present as an anterior mediastinal mass with involvement of the thymus and/or supraclavicular lymph nodes and affect preferentially young women. Median age of presentation is slightly older in PMBCL (35 years) than in cHL-NS (30 years) . The histopathological features of PMBCL include a diffuse proliferation of large cells with clear abundant cytoplasm and fine compartmentalizing sclerosis. Reed-Sternberg-like cells may be present [5, 6], and distinction from cHL-NS can sometimes be difficult. The neoplastic cells in PMBCL express B-cell markers (CD20, CD79a, CD19, PAX5) and lack expression of HLA class I antigens and surface immunoglobulin (Ig). However, expression of Ig-associated transcription factors BOB1, OCT2, and PU1 is preserved in contrast to cHL [7, 8]. CD30 is expressed in 70% of cases and tumour cells are typically CD23 positive. Seventy per cent of PMBCL and 10% of cHL express the MAL protein linking them histogenetically to the thymic asteroid medullary B cells [9, 10]. EBV is absent in PMBCL.
In order to understand the concept of this new category of lymphoma, we will briefly review the diagnostic criteria for Burkitt lymphoma (BL) according to the updated WHO classification of lymphoid neoplasms.