Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas-A Reappraisal of Follicular Helper T-Cell Lymphomas.

Peripheral T-cell lymphomas (PTCLs) expressing multiple follicular T helper (TFH) cell-related antigens are now classified as TFH lymphomas (TFHL), including angioimmunoblastic, follicular, and not otherwise specified (NOS) types. CXCR5 is the TFH cell-defining chemokine receptor that, together with its ligand CXCL13, plays a critical role in the development of follicles and the positioning of TFH and B cells within follicles. A comprehensive immunomorphologic study was performed to investigate the expression pattern of CXCR5 in a large cohort of nodal PTCLs, particularly those with a TFH cell phenotype, and to compare its expression with six other TFH cell-related antigens. We found that CXCR5 is widely expressed in neoplastic TFH cells, except in TFHL-NOS, and represents a specific marker of this lymphoma entity. Our results suggest that CXCR5 directs the distribution of neoplastic T cells in the affected lymph nodes and may influence the formation of the pathognomic pathological FDC network.

Pattern of MEF2B expression in lymphoid tissues and in malignant lymphomas.

Myocyte enhancer binding factor 2 B (MEF2B) is a member of the evolutionary conserved transcription family MEF2. MEF2B has been shown to directly control biological activity of the B cell lymphoma 6 (BCL6) gene in germinal center (GC) B cells. To validate MEF2B as an immunohistochemical marker, we studied a large consecutive series of hyperplastic lymphoid tissues (n = 38) and malignant lymphoproliferative conditions (n = 471), including all major categories of B and T cell neoplasms. In hyperplastic lymphoid tissues, MEF2B staining revealed intense and crisp nuclear expression confined to GC B cells. Unlike BCL6, MEF2B was not detected in follicular T cells. In addition, weak nuclear staining of plasma cells was noted. MEF2B staining labeled neoplastic cells of follicular lymphoma both in common and variant cases as well as in bone marrow biopsies with high sensitivity, while it was almost consistently negative in marginal zone lymphoma. Consistent MEF2B expression was found in Burkitt lymphoma and nodular lymphocyte predominant Hodgkin lymphoma as well as in the large majority of cases of mantle cell lymphoma and diffuse large cell B cell lymphoma. MEF2B protein expression showed a statistically significant association with that of BCL6 in cases of diffuse large B cell lymphoma, not otherwise specified. We conclude that MEF2B is a valuable marker of normal GC B cells, potentially useful in differential diagnosis of small B cell lymphomas.