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AITL : Differential Diagnosis

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Differential Diagnosis of Angioimmunoblastic T-cell lymphoma (AITL) includes:

Atypical T-zone Hyperplasia (ATZH): It is seen in viral infections or autoimmune diseases. The nodal architecture is preserved with normal-appearing follicles and germinal centers. There is no expansion of follicular dendritic cell meshworks (unlike in AITL). The cellular infiltrate mimics that of AITL and includes small and medium-sized lymphocytes without atypia, plasma cells, immunoblasts, and activated lymphocytes. Immunophenotypically, there is a population of CD4+/CD8+ cells with scattered CD20+, CD25+, and CD30+ cells. T-cell receptor genes are not rearranged.

Peripheral T-cell Lymphoma, NOS: Both AITL and PTCL, NOS share many morphologic features. Both can have small to medium-sized lymphoid cells with no atypia, a polymorphic inflammatory background, vascular proliferation with prominent high-endothelial venules, nests of clear cells, and scattered Reed-Sternberg-like cells. In addition, immunoreactivity for CD10, BCL6, CXCL13, ICOS, and PD1 in T cells may be seen in both conditions. The diagnosis of AITL is favored by the presence of CD21+ meshwork of follicular dendritic cells, open and distended peripheral cortical sinuses, and arborizing high endothelial venules.

Hodgkin Lymphoma: Many cases of AITL show numerous EBV+ B cells resembling Reed-Sternberg cells. Moreover, these cells have the immunophenotype of Reed-Sternberg cells (CD15+, CD30+, CD20+) and harbor EBV (positive for EBER, LMP-1). However, in contrast to classic Hodgkin lymphoma, AITL shows clonal rearrangement of T-cell receptor genes.

T-cell/Histiocyte-rich Large B-cell Lymphoma (THRLBCL): In THRLBCL, the background infiltrate is not polymorphic, unlike AITL. There are no expanded networks of FDCs. Large B-cell blasts are CD30- and EBV-. The T-cell receptor genes are not rearranged.

This image of AITL shows a polymorphic infiltrate of small to medium-sized lymphocytes (neoplastic cells) admixed with neutrophils, eosinophils, plasma cells, dendritic cells, histiocytes, and epithelioid cells.

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