B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology

Antonino Carbone, Annunziata Gloghini, Antonella Aiello, Adele Testi, Antonello Cabras

Research output: Contribution to journalArticlepeer-review


Published in September 2008, the updated World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues introduces provisional borderline categories for lymphoma cases that demonstrate overlapping clinical, morphological, and/or immunophenotypic features between well-established entities. These overlapping features pose real diagnostic challenges especially in identifying atypical cases of diffuse large B-cell lymphoma, Hodgkin lymphoma, and Burkitt lymphoma. Lymphoma cases showing borderline features between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma are not included within the borderline categories provisionally recognized by the updated classification. Within the borderline categories, there are cases combining features of primary mediastinal large B-cell lymphoma and classical Hodgkin lymphoma. Many of these cases resemble classical Hodgkin lymphoma but have a large number of tumor cells expressing CD20, CD45, and B-cell transcription factors. Alternatively, these cases may resemble primary mediastinal large B-cell lymphoma but contain tumor cells resembling Reed-Sternberg cells and displaying an aberrant phenotype such as CD20-, CD15-/+ CD45+, CD30+, Pax5+, OCT2+/-, and BOB1+/-. Another new borderline category defining B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, represents a biologically heterogeneous group. Cases with morphologic features intermediate and with CD10/BCL6 coexpression should be placed in diffuse large B-cell lymphoma/Burkitt lymphoma category if tumor cells also show strong BCL2 staining and/or a Ki67 proliferation index of less than 90%. When MYC rearrangements are present in these cases, the lymphomas often have atypical features, including concurrent rearrangements of BCL2 and/or BCL6 genes (so-called double/triple-hit lymphomas) and more aggressive behavior. For the provisional borderline categories, unresolved issues include understanding molecular pathogenesis and defining an effective treatment.

Original languageEnglish
Pages (from-to)621-631
Number of pages11
JournalHuman Pathology
Issue number5
Publication statusPublished - May 2010


  • "Gray zone" lymphomas
  • B-cell lymphoma
  • Borderline lymphomas
  • Hodgkin lymphoma
  • Pathogenesis
  • Pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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