T cell-rich lymphoid infiltrates with large B cells: a review of key entities and diagnostic approach

Abstract

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.

A Rare Case of Angioimmunoblastic T-Cell Lymphoma with Epstein-Barr Virus-Negative Reed-Sternberg-Like B-Cells, Chylous Ascites, and Chylothorax

“…Postmortal examination of an enlarged lymph node showed typical features of AITL, including effacement of nodal architecture with “burn out” lymphoid follicles (pattern II), proliferation of arborizing high endothelial venules, and the infiltration of CD4-positive atypical small T-lymphocytes with TFH phenotype [7]. The 2016 revision of the World Health Organization classification of lymphoid neoplasms introduces the umbrella term “nodal T-cell lymphomas with T-follicular helper phenotype,” which includes AITL, follicular T-cell lymphoma, and nodal PTCL with a TFH phenotype.…”

“…Identification of RS-like B-cells in subtypes of PTCL has led to a diagnostic dilemma as classical Hodgkin lymphomas are also characterized by a polymorphous background infiltrate. However, for AITL, identification of typical immunomorphological features such as proliferation of arborizing high endothelial venules and infiltration of atypical T-lymphocytes, negative PAX-5 immunostaining, and expression of CD3 and CD4 on a subset of RS-like B-cells can be used to avoid misdiagnosis [7, 14]. …”

“…EBV infection promotes survival of B-cells which subsequently undergo clonal expansion. Proliferation of B-cells may ultimately lead to development of a secondary malignant B-cell lymphoma [6, 7]. Recently, three cases of AITL with EBER-ISH-negative RS-like B-cells have been described [8].…”

“…Although EBV is not believed to play a primary role in AITL oncogenesis, it potentially contributes to establishing a clonal or oligoclonal B-cell population, including Reed-Sternberg-like B-cells (RS-like B-cells) in combination with an expanding T-cell population with tumorous behavior [5–7]. Reports of clonal and oligoclonal B-cell populations in EBV-negative AITL suggest that other mechanisms than EBV infection contribute to expansion of the B-cell population in AITL [6, 8].…”

Rozpoznawanie i leczenie chorych na chłoniaka rozlanego z dużych komórek B

“…Rzadziej diagnostykę różnicową DLBCL uzupełnia się o badania molekularne, które pozwalają na ocenę klonalności komórek limfoidalnych oraz różnicowanie trudnych diagnostycznie przypadków zmian chłoniakowych od odczynowych. Poszukiwanie aberracji cytogenetycznych, w tym klasyczną metodą prążkową, metodą FISH i/lub z użyciem badań molekularnych, jest najczęściej wykorzystywane do monitorowania choroby resztkowej (MRD, minimal residual disease) [27,44].…”