Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a
protein upregulated in cultured cells treated with
tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of
tumor cells in 4 of 4 cases (100%) of
follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of
histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising
follicular lymphoma,
small lymphocytic lymphoma,
mantle cell lymphoma, or marginal zone
lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical
Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant
Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large
B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of
diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of
Burkitt lymphoma, and in 1 of 19 cases (5%) of
anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than
TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large
B-cell lymphoma from those of its morphologic and immunophenotypic mimic,
diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and
histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical
Hodgkin lymphoma and primary mediastinal (thymic) large
B-cell lymphoma serves to distinguish these
tumors from other large cell
lymphomas in routine clinical practice.