A 63-year-old man presents with fever, night sweats, and fatigue. On examination he was found to have generalized peripheral lymphadenopathy. Excisional biopsy of his right inguinal lymph node was performed. Histology and immunohistochemical staining are shown below. In addition, the atypical small- medium-sized cells were positive for CD5, CD10, BCL6 (partial staining), and CXCL13 and were negative for CD20, PAX5, and cyclin D1. Scattered large CD20/PAX5-positive cells were EBV-positive by in situ hybridization.
The correct answer is ...
Angioimmunoblastic T-cell lymphoma.
The lymph node architecture is partially effaced by an abnormal lymphocyte population expanding the paracortex (Figure 1: H&E1). The lymphocytes are small to medium in size and have slightly irregular nuclear contours, inconspicuous nucleoli, and abundant clear cytoplasm. They are associated with prominent vasculature and arborized high endothelial venules (HEV) (Figure 2: H&E2). The abnormal lymphocytes often form small clusters around follicles and HEV and are accompanied by a polymorphous background of small reactive lymphocytes, plasma cells, eosinophils, and histiocytes (not shown in image). They usually express the pan-T-cell antigensCD2, CD3 and, CD5, have variable loss of CD7, and are almost always CD4-positive and CD8-negative. In contrast to other types of T-cell lymphoma, loss of pan–T-cell antigen expression is an uncommon finding in AITL. The expression of T follicular helper (TFH) cell markers such as CD10, BCL6, CXCL13, CD279, and ICOS represents an important adjunct in the diagnosis of AITL and provides further evidence that AITL derives from TFH cells. In addition, they are associated with disorganized, largely disrupted, CD21-positive follicular dendritic cell meshworks surrounding the prominent vessels, which is a diagnostic hallmark of AITL. Finally, EBV is detected by in situ hybridization in 80% to 96% of lymph nodes involved by the disease. In most cases, the EBV-infected cells represent transformed B cells. These morphologic and immunoarchitectural features support the diagnosis of AITL. Per WHO5 classification this lymphoma would be classified as nodal TFH cell lymphoma, angioimmunoblastic-type. Per ICC classification this lymphoma would be classified as follicular helper T-cell lymphoma, angioimmunoblastic type.
Peripheral T-Cell lymphoma, not otherwise specified (PCTL-NOS) encompasses all mature T-cell lymphomas lacking specific features that would allow categorization within any of the better defined “specific” subtypes of other mature T-cell lymphoma described in the WHO classifications. The presence of morphologic features typical of AITL coupled with a TFH phenotype would support the diagnosis of AITL and exclude the diagnosis of PTCL-NOS.
Reactive lymphoid hyperplasia of lymph node can have overlapping features with early involvement by AITL. Absence of atypical T-cells with abundant clear cytoplasm that are positive for TFH cell markers and lack of disrupted follicular dendritic cell meshworks favor reactive lymphoid hyperplasia over AITL. Although absence of a T-cell receptor gene rearrangement would support reactive lymphoid hyperplasia, clonal T-cell receptor gene rearrangements can occasionally be seen in reactive conditions, so the presence of a clonal T-cell receptor gene rearrangement does not necessarily support the diagnosis of malignant lymphoma of T-cell lineage.
Classic Hodgkin lymphoma (CHL), mixed cellularity type — In some cases of AITL, the presence of scattered EBV-positive B cells that have some overlapping features with some of which can acquire Hodgkin/Reed Sternberg (HRS) cells (variable CD15+, CD30+, variable CD20+) may mimic CHL. Because AITL cases may show minimal cytologic atypia of T cells, the distinction from CHL may be difficult. CHL lacks neoplastic T cells with clear cytoplasm and shows no increase in HEV or FDC. As above, although absence of a T-cell receptor gene rearrangement would support CHL, the presence of a clonal T-cell receptor gene rearrangement does not necessarily support the diagnosis of malignant lymphoma of T-cell lineage.
Mazen Osman, M.B., B.Ch.
Ellen McPhail, M.D.
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science