Angiodestruction and Tissue Necrosis of Skin-Involving CD56+ NK/T-Cell Lymphoma Are Influenced by Expression of Cell Adhesion Molecules and Cytotoxic Granule and Apoptosis-Related Proteins

Abstract

We compared the expression of cell adhesion molecules (CAMs), cytotoxic granule proteins, and apoptosis-related proteins by immunohistology and in situ terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end labeling (TUNEL) of 10 cases of cutaneous CD56+ NK/T cell lymphoma with and 6 cases without angiodestruction. Lymphoma cells in cases with angiodestruction frequently expressed CAMs CD2, CD11a, and CD49d and their ligands CD58, CD54, and CD106 and were positive for CD122 and cytotoxic granule proteins TIA1, perforin, and granzyme B. Lymphoma cells in cases without angiodestruction mostly were negative for CD2, CD58, CD54, CD106, and TIA1 and weakly positive for perforin and granzyme B. In the TUNEL method, mean apoptotic indices (AI) for cases with angiodestruction showed a higher percentage than those without angiodestruction. CD95L, CD95, apoptosis-induced cysteine protease CPP32, apoptosis-promoting protein Bax, and proliferating marker (MIB1) frequently were positive in the lymphoma cells of cases with angiodestruction, but there was no expression of apoptosis-inhibitor protein Bcl2. In most cases without angiodestruction, lymphoma cells were positive for CD95L and Bax and negative for CD95, CPP32, and MIB1. CAMs and the 3 cytotoxic granule proteins and an apoptosis pathway might be important factors in the paracrine and autocrine mechanisms of tissue necrosis in cutaneous CD56+ NK/T cell lymphoma.

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

“…Despite the widespread prevalence of EBV infection, EBV has been directly implicated in the development of only two malignancies observed in relatively restricted geographic areas: Burkitt's Lymphoma in East Africa and nasopharyngeal carcinoma in Southern China. It has also been closely associated to Hodgkin's Disease, thymic lymphoepithelioma, opportunistic B-cell lymphomas, pleural B-cell lymphomas or pyothorax associated B-cell lymphomas, opportunistic T-cell and NK-cell lymphomas in immunodeficiencies, primary nasal T-cell and NK-cell lymphomas, gastric carcinoma, and most recently, invasive breast carcinoma (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

Vascular lesion in a patient of chronic active Epstein-Barr virus infection with hypersensitivity to mosquito bites: vasculitis induced by mosquito bite with the infiltration of nonneoplastic Epstein-Barr virus–positive cells and subsequent development of natural killer/T-cell lymphoma with angiodestruction

“…The close association between HMB and NK cell proliferative disorders/ lymphomas has been known [8,9]. The affinity of EBVinfected lymphoid cells to blood vessels has been previously reported in EBV-positive NK/T-cell lymphomas [8,10,11]. The term angiocentric or angiodestructive pattern is often used to describe these lesions of the lymphoma tissue.…”

Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

“…The frequency of CD2, CD54, CD58 and CD106+ cases is higher among NKTCL with angiodestruction, as compared with those without [131]. Finally, the integrin subunits alpha2 (CD49b) and alpha M (CD11b) are expressed at a significantly higher level on lymphoma cells in NKTCL with angioinvasion than in those without [134].…”

“…Although the exact mechanism is unknown, previous studies revealed that the presence of cytotoxic granule proteins, and the expression of apoptosis related and cell adhesion molecules on the neoplastic NK-cells are relevant factors [129][130][131][132][133][134].…”

“…In addition, ANKCL patients have high serum levels of soluble FasL and ANKCL cells express the FasL protein [129]. Lymphoma cells from cases with angiodestruction also express frequently FasL, Fas, CPP32 (apoptosis-induced cysteine protease 32), the apoptosispromoting protein BAX, and the Ki67/MIB1 (mindbomb E3 ubiquitin protein ligase 1) nuclear proliferating marker, whereas in cases without angiodestruction, the neoplastic cells are frequently positive for FasL and BAX, and negative for Fas, CPP32, and Ki67/MIB1 [131].…”