Date Published: November 14, 2011
Publisher: Hindawi Publishing Corporation
Author(s): Xingcao Nie, Rekha Bhat, Essel Dulaimi Al-Saleem, Eric C. Vonderheid, J. Steve Hou.
Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor stromal cells in a variety of malignancies. Our study explores thymidine phosphorylase expression in lymph nodes (LNs) from patients with mycosis fungoides (MF) or Sézary syndrome (SS). In MF/SS, the LNs may have a pathologic diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL and benign nodes, thymidine phosphorylase staining was noted only in macrophages, dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase expression was also noted in subsets of intermediate to large neoplastic T cells. Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations. Similar results were noted in the skin and in LN-MF with large cell transformation. Other T-cell lymphomas were also examined (total 7 cases); only enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T lymphocytes. We demonstrated that thymidine phosphorylase staining is present in neoplastic T cells in mycosis fungoides. The exact mechanism needs further investigation.
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous T-cell lymphomas and represent clonal proliferations of neoplastic CD4+ T cells. MF initially develops in an indolent fashion as a skin-confined disease. However, with progressive disease, malignant T cells involve skin-associated lymph nodes (LNs), thereby indicating a higher clinical stage . The presence of circulating neoplastic cells in the peripheral blood is the hallmark of SS. Lymphadenopathy in MF/SS ranges from dermatopathic lymphadenopathy (DL), a reactive pattern associated with various chronic skin diseases, to clearcut involvement by malignant T cells that results in partial or complete effacement of lymph node structure (MF-LN). Smaller numbers of atypical or neoplastic cells may be found in DL, but the prognostic significance is unclear .
Experimental protocols were approved by the Institutional Review Board of Drexel University College of Medicine. Archived paraffin blocks with LNs from 51 patients with MF and SS (1991–2010) were used to construct a tissue microarray. Thirty-four of 51 MF/SS patients had a pathologic diagnosis of DL and 17 had partially or completely effaced LNs by MF or SS. Immunohistochemical (IHC) staining using antibodies to TP, CD68, CD21, CD3, and CD4 was performed. Nine cases of benign LNs were included as control. Archived unstained skin slides were also used to test TP expression from patients with MF in skin-confined stage (5 cases), MF-LN with large cell transformation (1 case), extranodal NK/T-cell lymphoma (1 case), peripheral T-cell lymphoma (2 cases), enteropathy-type T-cell lymphoma (1 case), angioimmunoblastic T-cell lymphoma (2 cases), and syringotropic cutaneous T-cell lymphoma (1 case).
In control LNs, TP staining was noted only in macrophages, dendritic cells, and endothelial lining cells, with a cytoplasmic and nuclear staining pattern. Small lymphocytes were negative for TP. A similar TP IHC staining pattern was noted in DL. Positive TP immunostaining was noted in 30% to 80% of intermediate to large neoplastic T cells in all MF-LN cases with a predominantly cytoplasmic staining pattern (Figure 1). Small lymphocytes were negative for TP, and macrophages, dendritic cells, and endothelial lining cells were again positive for TP. Concurrent CD68 and CD21 staining supported the above observations (Figure 1). IHC staining in MF-skin (Figures 2(a)–2(c)) and in MF-LN with large cell transformation (Figure 2(d)) showed a similar staining pattern. Positive TP staining was noted in the neoplastic T cells in one case of enteropathy-type T-cell lymphoma (Figure 3). In other lymphoma cases (extranodal NK/T-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and syringotropic cutaneous T-cell lymphoma) positive TP staining was only noted in macrophages and endothelial cells.