Composite Epstein-Barr Virus-associated T-lymphoblastic and Peripheral T-cell Lymphomas: A Clonal Study

Abstract

A 30-year-old woman was diagnosed with T-lymphoblastic lymphoma (T-LBL) that harbored a clonal Epstein-Barr virus (EBV) genome. At relapse, axillary lymph node adenopathy, which was diagnosed as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), was detected. Southern blot analyses of the T-cell receptor and EBV genome revealed that the T-LBL and PTCL-NOS were clonally identical. We previously showed that CD21 acted as an entry molecule that allowed EBV into the patient's T-LBL cells. Interestingly, the PTCL-NOS cells lacked CD21 expression. Our case suggests that EBV might infect immature CD21-positive T-cells, and CD21-negative PTCL-NOS might subsequently arise through phenotypic changes.

Keywords: CD21; Epstein-Barr virus; T-lymphoblastic lymphoma; composite lymphoma; peripheral T-cell lymphoma.

Figure 1.

Computed tomography (CT) and histopathological findings of the patient at relapse. A: CT image of the patient obtained at relapse. The red arrow indicates the left axillary lymph nodes resected during the postmortem examination. B-G: Histopathological findings of the peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), after it was resected from the axillary lymph nodes. B: Hematoxylin and Eosin staining (×400); C, D: Immunohistochemistry of CD4 (C) and TdT (D) (×600); E: In situ hybridization of Epstein-Barr virus (EBV)-encoded mRNA (×600). F: Double immunohistochemical staining of CD4 and EBER. The CD4- and EBER-positive cells were stained red and brown, respectively (×600). G: Immunohistochemistry of CD21 (×600).

Figure 2.

Genomic analyses of the T-cell receptor (TCR) and EBV. A: Southern blot analyses using a Cβ2 probe. The arrows indicate rearranged bands. DNA was digested with BamHI. Lane 1: peripheral lymph nodes, lane 2: pleural effusion, lane 3: MD901 (the negative control). B, C: TCR gene rearrangement of Vβ/Jβ1/Jβ2 in cells from the peripheral lymph nodes (B) or pleural effusion (C). The polymerase chain reaction was conducted using 23 Vβ primers and 9 Jβ primers, as described previously (9). The arrows indicate the clonal peaks. The same clonal peaks were seen in (B) and (C), indicating that these cells were identical. 1: negative control, 2: positive control, 3: patient’s sample. D: Southern blot analyses of the EBV genome. The EBV1 and EBV2 fragments were used as probes. DNA was digested with BamHI, EcoRI, and HindIII. Lane 1: peripheral lymph nodes, lane 2: pleural effusion, lane 3: MD901 (the negative control). E: Schematic diagram showing a putative mechanism that might have caused the EBV-induced T-cell malignancies seen in this patient. EBV-infected, CD4-positive, CD8-positive immature T-cells, which also expressed CD21, were present in the patient’s thymus. The cells developed into T-lymphoblastic lymphoma (T-LBL). After treatment, including allogeneic stem cell transplantation, CD4-positive, CD8-negative PTCL developed through phenotypic changes. The PTCL cells were negative for CD21, which was the molecule responsible for the entry of EBV into the T-LBL cells in this patient, but EBV had already infected the PTCL cells.