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T cell-rich lymphoid infiltrates with large B cells: a review of key entities and diagnostic approach
  1. Chee Leong Cheng1,
  2. Simon O'Connor2
  1. 1Anatomical Pathology Department, Singapore General Hospital, Singapore, Singapore
  2. 2Haematological Malignancy Diagnostic Service, Centre for Molecular Pathology, The Royal Marsden Hospital, Sutton, London, UK
  1. Correspondence to Dr Chee Leong Cheng, Anatomical Pathology Department, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore 169856, Singapore; cheng.chee.leong{at}


Accurate diagnostic interpretation of a lymphoid population composed predominantly of small T cells, together with smaller numbers of large B cells, with or without a nodular architecture, is a common problem faced by the histopathologist. The differential diagnosis of this histological pattern is wide, ranging from reactive conditions such as drug reactions and viral infections, through borderline entities such as immunodeficiency-related lymphoproliferative disorders to lymphomas. The latter includes entities where the large B cells are primarily neoplastic (classical and nodular lymphocyte-predominant Hodgkin lymphomas and T cell/histiocyte-rich large B cell lymphoma) as well as T cell lymphomas such as angioimmunoblastic T cell lymphoma where the large B cells represent an epiphenomenon and may or may not be neoplastic. Several rare variants of these conditions, and the fact that treatment can significantly modify appearances, add to the diagnostic difficulty of these pathological entities. Unlike monomorphic lymphoid infiltrates, the histological pattern of T cell-rich proliferation with large B cells requires close evaluation of the inter-relationship between B cells and T cells, follicular dendritic cells and sometimes other inflammatory cells. Epstein-Barr virus plays a key role in several of these scenarios, and interpreting not only its presence but also its distribution within cellular subgroups is essential to accurate diagnosis and the avoidance of some important diagnostic pitfalls. An understanding of normal immunoarchitecture and lymphoid maturational pathways is also fundamental to resolving these cases, as is a knowledge of their common patterns of spread, which facilitates correlation with clinical and radiological findings.


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  • Handling editor Cheok Soon Lee

  • Contributors CLC wrote the manuscript. SO provided guidance and significant input for refinement of the work.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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