Aberrant Expression of the Dendritic Cell Marker TNFAIP2 by ... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

Aberrant Expression of the Dendritic Cell Marker TNFAIP2 by the Malignant Cells of Hodgkin Lymphoma and Primary Mediastinal Large B-Cell Lymphoma Distinguishes These Tumor Types From Morphologically and Phenotypically Similar Lymphomas

Kondratiev, Svetlana MD*; Duraisamy, Sekhar PhD†; Unitt, Christine L. BA*; Green, Michael R. PhD‡; Pinkus, Geraldine S. MD*; Shipp, Margaret A. MD‡; Kutok, Jeffery L. MD, PhD*; Drapkin, Ronny I. MD, PhD†; Rodig, Scott J. MD, PhD*

*Department of Pathology, Brigham & Women’s Hospital

†Department of Pathology, Dana-Farber Cancer Institute

‡Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Scott J. Rodig, MD, PhD, Department of Pathology, Amory 3rd Floor, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 (e-mail: [email protected]).

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Abstract

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.