Aggressive peripheral T-cell lymphomas containing Epstein-Barr viral DNA: a clinicopathologic and molecular analysis.

The Epstein-Barr virus (EBV) has been shown to be associated with posttransplant lymphoma, Hodgkin's disease, and T-cell lymphoma, in addition to African Burkitt's lymphoma. In a retrospective study of 56 consecutive cases of T-cell lymphoma, EBV DNA was found by Southern blot and in situ DNA hybridization in 10 (20%) of 50 peripheral T-cell lymphomas, but in none of six cases of T-lymphoblastic lymphoma. Peripheral T-cell lymphomas containing EBV DNA could be subclassified into three categories according to histology and immunophenotypic studies: (1) T-cell lymphoma of the helper phenotype, five cases. Two cases had histologic features resembling angioimmunoblastic lymphadenopathy (AILD). (2) T-cell lymphoma of the cytotoxic/suppressor phenotype, four cases. AILD-like features could also be recognized in two cases. Reed-Sternberg-like giant cells were identified in three cases designated Hodgkin-like T-cell lymphoma. (3) Angiocentric T-cell lymphoma or lymphomatoid granulomatosis in one case, initially affecting the skin and nose; no T-cell subset could be defined. Six of the eight EBV DNA-positive patients tested for serum EBV antibodies had elevated titers of IgG antiviral capsid antigen (greater than 640) and/or early antigen (greater than 10). From combined studies of Southern blot hybridization by using EBV termini fragment probe and in situ DNA hybridization, the EBV genomes appeared to be clonotypically proliferated in the neoplastic T cells. The patients in all three groups usually had prolonged fever preceding the diagnosis, hepatosplenomegaly, an aggressive clinical course, and poor response to chemotherapy; nine died with a median survival of only 8 months. We propose that these EBV-associated aggressive T-cell lymphomas, like human T-cell leukemia/lymphoma virus-positive T-cell lymphoma, have characteristic clinicopathologic features and should be treated as a separate disease entity.     

Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin's lymphoma.

Individuals infected with the human immunodeficiency virus (HIV) have an increased incidence of high-grade B-cell lymphoma. In many instances, these lymphomas contain Epstein-Barr viral (EBV) genomes. To investigate the role of EBV in development of HIV-related lymphoma, benign fixed lymph node biopsies from normal individuals and HIV-infected individuals with persistent generalized lymphadenopathy (PGL) were analyzed for EBV sequences by polymerase chain reaction and in situ DNA hybridization techniques. EBV DNA was not detected in any of 16 benign lymph node biopsies from normal individuals, but could be detected from 13 of 35 PGL biopsies. The EBV-infected cells were present in both follicular and interfollicular areas and in both small and large lymphoid cells. The presence of detectable amounts of EBV DNA in the 13 PGL biopsies was associated with an increased incidence of concurrent lymphoma at another site (n = 3) or development of lymphoma in time (n = 2). In contrast, only 1 of 22 individuals with EBV-negative PGL biopsies developed lymphoma in time (P less than .05). EBV was detected in all five lymphomas in which tissue was available for subsequent analysis, including the lymphoma that developed in the individual without EBV in his previous PGL biopsy. These findings support the hypothesis that EBV plays a role in development of some HIV-related lymphomas. Detectable EBV lymphoproliferations occur in a few PGL biopsies and are associated with a significant risk of EBV DNA-positive non-Hodgkin's lymphoma.     

Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma.

We studied 23 cases of angioimmunoblastic lymphadenopathy (AILD) and AILD-like lymphoma for evidence of Epstein-Barr virus (EBV) using the polymerase chain reaction (PCR) and in situ hybridization studies. EBV nucleic acid sequences were found by either PCR or in situ hybridization in 96% of the cases. There was a wide range in the number of EBV-positive cells among the different cases as detected by in situ hybridization. The EBV-positive cells most often possessed nuclei of intermediate to large size. Double-labeling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed the B-lineage antigen CD20 (as detected by L26), with a minority of the EBV-positive cells stained for the T-lineage associated antigen, CD43 (as detected by Leu 22). The abnormally high amounts of EBV found in AILD and AILD-like lymphoma may be a reflection of decreased immunocompetence in these patients. The presence of EBV-positive B cells may explain the presence of B-cell clones found by others as well as the paradoxical occurrence of B-cell lymphoma in a primary T-cell lymphoproliferative disorder.     

Simultaneous phenotypically distinct but clonally identical mucosa-associated lymphoid tissue and follicular lymphoma in a patient with Sj?gren's syndrome.

A 44-year-old woman with a 12-year history of Sj?gren's syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.     

Characterization of posttransplant lymphomas that express T-cell- associated markers: immunophenotypes, molecular genetics, cytogenetics, and heterotransplantation in severe combined immunodeficient mice

Immunosuppressed individuals are at high risk for the development of hematologic malignancies. The typical lymphomas arising in organ transplant recipients are B-cell non-Hodgkin's lymphomas that contain Epstein-Barr virus (EBV) DNA sequences. We investigated the characteristics of posttransplant lymphomas that lacked expression of the usual markers associated with EBV transformation. We describe four large-cell lymphomas seen recently at our institution. Two of these four cases were CD4+, one was CD8+, and in one staining for CD4 and CD8 expression was not performed. One CD4+ lymphoma was a CD30+, EBV- large- cell lymphoma from a 65-year-old kidney transplant recipient, the second was an EBV+ large-cell lymphoma from a 25-year-old heart transplant patient. Two T-cell lymphomas were EBV+ and had clonal T- cell receptor beta gene rearrangements. The other two lymphomas expressed T-cell markers CD4 and CD43, and lacked expression of B-cell markers CD19, CD20, CD21, CD22, CD23, and surface Ig. Both CD4+ lymphomas were tumorigenic after their heterotransplantation into severe combined immunodeficient (SCID) mice. Cytogenetics, immunophenotyping, and genotyping of the secondary tumors from SCID mice showed their clonality and identity with the patients' primary tumors. Novel CD4+ lymphoma cell lines, LH521/4 and LK418/4, were established from tumors that had been passaged in SCID mice. An immunodeficient environment may facilitate the growth of these T-cell or biphenotypic lymphomas; the etiology of their genesis can include transformation with EBV and other, as yet unidentified mechanisms.     

Epstein-Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis

Objective. A causative role for Epstein-Barr virus (EBV) in the development of lymphoma in patients with rheumatoid arthritis (RA) has been proposed. We investigated the molecular features of EBV-positive diffuse large cell lymphomas in 2 patients with RA. Methods. Southern blot analysis for immunoglobulin gene rearrangements, terminal repeat analysis for clonality of the EBV genome, and double-labeling of the lymphoma cells by in situ hybridization and immuno-peroxidase staining were performed. Results. In both cases, double-labeling studies localized the EBV genome to the malignant B cells. Both neoplasms contained clonal immunoglobulin gene rearrangements and clonal EBV genomes. Conclusion. Our data indicate that EBV infection was an early step in the development of these neoplasms. The findings further extend knowledge on the similarity of this subset of lymphomas to posttransplantation lymphomas and emphasize the role of immunosuppression in their genesis.     

High-grade T-cell lymphoma complicating B-cell chronic lymphocytic leukemia: an unusual manifestation of "Richter's syndrome"

Approximately 3% of patients with B-cell chronic lymphocytic leukemia (CLL) develop a high-grade large-cell lymphoma consistent with Richter's Syndrome. In most cases, these lymphomas are of B-cell origin and are believed to arise by clonal evolution from the CLL cells. We present a case of a patient with a 10-year history of B-CLL who developed an aggressive large-cell lymphoma, confirmed by immunophenotype to be of T-cell origin. We suggest that in patients with CLL, immunodysregulation can result in the proliferation of T cells, which may mutate and result in the development of a new malignant clone.     

Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders

The posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22 patients for activating alterations involving the bcl-1, bcl-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor gene. We correlated the results of these studies with the morphology of the lesions, their clonality based on Ig heavy and light chain gene rearrangement analysis, and the presence and clonality of EBV infection. We found that the PT-LPDs are divisible into three distinct categories as follows: (1) plasmacytic hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly always polyclonal, usually contain multiple EBV infection events or only a minor cell population infected by a single form of EBV, and lack oncogene and tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly always monoclonal, usually contain a single form of EBV, and lack oncogene and tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple myeloma: present with widely disseminated disease, are monoclonal, contain a single form of EBV, and contain alterations of one or more oncogene or tumor suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene rearrangement). The PT-LPDs are divisible into three categories exhibiting distinct morphologic and molecular genetic characteristics. Alterations involving the N-ras and c-myc proto- oncogenes and the p53 tumor suppressor gene may play an important role in the development and/or progression of the PT-LPDs.     

Polyclonal rearrangements of the T-cell receptor β-chain in fatal angioimmunoblastic lymphadenopathy

Genomic rearrangement of germline T-cell antigen receptor (TcR) and immunoglobulin (Ig) genes was studied by Southern blot analysis in seven patients with angioimmunoblastic lymphadenopathy (AILD). In three cases clinically suspected of transformation into malignant lymphoma, hybridization with the TcRβ probe showed markedly dimished intensity in the 11.5 kb germline band after Eco RI digestion and normal germline configuration after Hind III and Bam HI digestion, indicating polyclonal T cell rearrangements. A clonal rearrangement of the TcRβ gene was detected in only one case at initial biopsy. No monoclonal rearrangement of Ig genes was observed. These data show that in some cases of AILD disease progression is indicated by polyclonal TcR rearrangements and not by outgrowth of a malignant clone, supporting the concept of AILD as an immunoregulatory disorder.     

Diffuse large cell lymphoma in a patient with hairy cell leukemia: immunoglobulin gene analysis reveals separate clonal origins

A 75-year-old man with hairy cell leukemia (HCL) was found to have an immunoblastic lymphoma of the small bowel. Immunologic and genotypic characterization of these neoplasms revealed both the HCL and the immunoblastic lymphoma to be of the B cell lineage. The HCL expressed the HCL-associated antigens detected by the monoclonal antibodies HC-1 and HC-2, whereas the immunoblastic lymphoma failed to react with these antibodies. In addition, surface immunoglobulin light chains could not be accurately determined for the hairy cells, whereas the immunoblastic lymphoma was shown to express only kappa immunoglobulin light chains. These immunophenotype differences were compatible with either the clonal evolution of the HCL into the immunoblastic lymphoma or a separate clonal origin for these two neoplasms. An analysis of tumor DNA by Southern blot hybridization revealed different heavy-chain and kappa light-chain gene rearrangements in these two malignancies. Thus the occurrence of the large cell lymphoma most likely represents the emergence of a second clonally unrelated B cell malignancy.     

In situ follicular lymphoma associated with overt B- or T-cell lymphomas in the same lymph node

In situ follicular lymphoma (FL) is usually an incidental finding in otherwise reactive lymph node [1–3]. However, it may be associated with overt FL, or with lymphomas other than FL or with other malignancies,in other sites or, less commonly, in the same lymph node [2,4–8]. Here we describe two cases of in situ FL, one with concurrent overt FL(Case 1), and one with concurrent peripheral T-cell lymphoma (PTCL),NOS (Case 2) in the same lymph node. Immunohistochemistry, polymerase chain reaction for B and T-cell clonality, and double-staining chromogenic in situ hybridization for BCL2 translocation were performed.In both cases, the in situ FL foci were characterized by strong expression of BCL2 and CD10 in the germinal center B cells of the affected follicles. Case 1 showed the concurrence of an overt B-cell FL with IgH@ rearrangement and expression of B-cell markers, but not BCL2. Case 2 demonstrated the concurrence of a PTCL, NOS with TCRG@ rearrangement and expression of T-cell markers. In conclusion,the association of in situ FL with PTCL expands the spectrum of lymphoproliferations that may coexist with in situ FL and suggests that in situ FL may not behave like a simple precursor for overt FL.     

Epstein-Barr virus infection and associated products (LMP,EBNA2, vIL-10) in nodal non-Hodgkin's lymphoma of human immunodeficiency virus-negative Japanese

Sixty cases of B-cell nodal non-Hodgkin's malignant lymphoma (B-ML), and 46 cases of T-cell nodal lymphoma (T-ML) were surveyed for Epstein-Barr virus (EBV) genomes, RNA, and associated proteins. We used a Southern blot analysis, polymerase chain reaction (PCR), and EBV-encoded small RNA-1 (EBER-1) in situ hybridization to investigate the presence of EBV. We performed an immunohistochemical study on EBV-related oncoproteins, such as EBV-determined nuclear antigen-2 (EBNA-2), latent membrane protein (LMP), and viral interleukin-10 (vIL-10). In addition, we also analyzed the terminal repetitive sequence of EBV (EBV-TR) to investigate the EBV-infected cell clonality. Non-Hodgkin's lymphomas were grouped into three types by number of EBV-infected cells: I) almost all lymphoma cells showed an EBV presence; II) some scattered lymphoma cells showed an EBV presence; and III) only a few cells showed such a presence, which was probably due to a latent EBV infection. In 25 of 60 B-MLs, EBV-infected cells were found; 7 were type I, 1 was type II, and 17 were type III. In 27 of 46 T-MLs, EBV-infected cells were found; no cases were type I, 5 cases were type II, and 22 cases were type III. Seven B-MLs and 3 T cell lymphomas showed clonal TR bands. Expression of EBNA-2 was found in only three B-MLs, whereas LMP was seen in four B-MLs and six T-MLs. All EBNA-2/LMP-positive cases showed an EBV presence. In B-MLs, expression of EBNA-2 and LMP was detected in almost all lymphoma cells; In T-MLs, however, LMP was found in only a small portion of the lymphoma cells. Expression of IL-10 was closely associated with LMP. In summary, it was thus speculated that EBV infection was associated with the various states of lymphomagenesis. © 1996 Wiley-Liss, Inc.     

Use of cloned probes to detect Epstein-Barr viral DNA in tissues of patients with neoplastic and lymphoproliferative diseases

Cloned fragments of the Epstein-Barr virus (EBV) genome were used to examine tissues from 145 patients for the presence of EBV DNA by two techniques: (1) nucleic acid hybridization of cell spots from which the DNA had been extracted in situ and (2) hybridization of DNA that had been transferred to nitrocellulose by Southern blotting. EBV DNA was found in tissues from four adults and five children with American Burkitt's lymphoma, infectious mononucleosis, lymphoma following bone marrow transplant, central nervous system lymphoma, nasopharyngeal carcinoma, and fatal polyclonal B-cell lymphoma following mononucleosis; two patients also had chronic pneumonitis, failure to thrive, and abnormal immune function. Six of the nine patients whose tissues contained EBV DNA had a demonstrable or presumed associated immunologic disorder. EBV DNA was not found in normal tissues or in a variety of hematologic neoplasms and other disorders. Nucleic acid hybridization methods can be used for the routine examination of the association of EBV with lymphomas and other lymphoproliferative syndromes occurring in immunodeficient individuals.     

Chromosomes and surface markers in lymph node cells from 2 patients with AILD and IBL-like T-cell lymphoma

Chromosomes and surface markers in lymph node cells from 2 patients with angioimmunoblastic lymphadenopathy associated with dysproteinemia (AILD) or immunoblastic lymphadenopathy (IBL) and with IBL-like T-cell lymphoma, respectively, were examined before treatment. In the patient with AILD, a small clone with chromosome abnormality was found in lymph node cells although a surface marker study failed to demonstrate monoclonality. In this patient, the clinical and cytogenetic findings suggested a subtype of lymphoma with a mild clinical course and a benign histological appearance. In the patient with IBL-like T-cell lymphoma, a high percentage of metaphases showed chromosome abnormalities such as ring chromosomes. The clinical, immunological and cytogenetic findings suggested an aggressive type of lymphoma, even though the histologic appearance was similar to that of IBL.     

Fatal Epstein-Barr virus-associated hemophagocytic syndrome

A virus-associated hemophagocytic syndrome is characterized by high fever, liver dysfunction, coagulation abnormalities, pancytopenia, and a benign histiocytic proliferation with prominent hemophagocytosis in bone marrow, lymph node, spleen, and liver. We describe six Japanese children with fatal Epstein-Barr virus (EBV)-associated hemophagocytic syndrome. Five of the six patients had serologic evidence of primary EBV infection at the onset of their diseases. EBV genomes were detected in all the patients by Southern blot hybridization or the polymerase chain reaction. Furthermore, clonality analysis of the EBV genome showed that EBV-infected cells proliferated monoclonally or biclonally in three examined patients. In situ hybridization study using EBV- encoded RNA 1 (EBER1) showed that EBER1 was detected in one of two examined liver tissues, which localized in hepatocytes.     

A case of age-related EBV-associated B-cell lymphoproliferative disorder metachronously showing two distinct morphologic appearances, one of a polymorphic disease resembling classical Hodgkin lymphoma, and the other of a large-cell lymphoma

We report a case of age-related EBV-associated B-cell lymphoproliferative disorder (age-related EBV+ B-cell LPD) metachronously showing two distinct morphologic appearances: one of a polymorphic disease resembling classical Hodgkin lymphoma (CHL), and the other of a large-cell lymphoma. A 71-year-old man was admitted to the St. Marianna University Hospital because of fever and generalized lymphadenopathy. Right axillary lymph node biopsy revealed mixed cellularity classical Hodgkin lymphoma (MCHL). The patient was referred to the Tokyo Medical Center, where he was treated with chemotherapy and obtained CR. One year later, the patient again developed fever and generalized lymphadenopathy. Biopsy of the right cervical mass revealed a diagnosis of diffuse large B-cell lymphoma. The patient was treated with salvage chemotherapies and obtained the second CR. Two years later, the patient developed acute myeloid leukemia (AML). Although CR was achieved with chemotherapy, AML relapsed 5 months later and proved to be refractory. Two and a half years later, the patient developed right cervical lymph node enlargement. The biopsy again revealed diagnosis of MCHL. The patient died 2 months later. On reviewing all of the biopsy specimens, including the findings of immunohistochemistry and in situ hybridization, possibility of CHL was ruled out, because neoplastic giant cells resembling Hodgkin and Reed-Sternberg (HRS) cells were positive for both Oct2 and BOB.1, which has not been reported in CHL. Both HRS-like cells at the time of diagnosis of Hodgkin lymphoma and lymphoma cells at the time of diagnosis of non-Hodgkin lymphoma were positive for CD20 and EBV-encoded small RNAs. This case was finally diagnosed as having age-related EBV+ B-cell LPD. We report the case here as it underscores the difficulty in diagnosing age-related EBV+ B-cell LPDs and also suggests an important role of EBV in the pathogenesis of lymphoid neoplasms.     

Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma.

We describe the use of the Southern blot hybridization technique to diagnose B-cell lymphoma by detecting clonal immunoglobulin gene rearrangements in lymph node and other biopsy tissues. DNA was isolated from a wide variety of neoplastic and non-neoplastic specimens and analyzed for the presence of rearranged immunoglobulin genes using radiolabeled DNA probes specific for the heavy- and light-chain immunoglobulin constant region genes. Among the specimens examined, clonal immunoglobulin gene rearrangements were found only in biopsy samples of B-cell lymphoma and not in samples containing reactive lymphoid processes or non-B-cell cancers. In lymphomas, the presence of rearrangements for either the kappa or lambda light-chain gene correlated with expression of one or the other of these chains when cellular immunoglobulins could be detected by frozen-section immunophenotyping techniques. The analysis of immunoglobulin gene rearrangements offers several advantages over conventional diagnostic methods for lymphomas, including improved sensitivity in detecting minor populations of neoplastic lymphocytes composing as little as 1% of the total cell population. In addition, clonal immunoglobulin gene rearrangements are demonstrable in a subset of lymphomas that lack detectable surface or cytoplasmic immunoglobulin, thus offering positive evidence for both malignancy and the B-cell origin of these tumors. Our studies indicate that detection of immunoglobulin gene rearrangements is a valuable method for diagnosis and classification of various lymphoproliferative disorders that are difficult to evaluate histologically or that lack distinctive antigenic markers.     

NK-cell intravascular lymphomatosis--a mini-review

The majority of cases of intravascular lymphomatosis (IVL) is derived from B cells. However, IVL may also arise from T cells, or more rarely NK cells. The clinicopathological findings in six cases of NK-cell IVL (NK-IVL), including one new case, were summarised and compared with B-cell IVL (B-IVL) and T-cell IVL (T-IVL). Earlier onset of disease and female predominance were found in NK-IVL. NK-IVL was typically Epstein-Barr virus (EBV)-positive, whereas EBV was rarely detected in B-IVL. Cutaneous manifestations were common in NK-IVL with constant EBV infection. B-IVL showed a more favourable prognosis than T- or NK-IVL. Irrespective of immunophenotype, however, IVL showed a less favourable prognosis than ordinary lymphomas within the same immunophenotype. In summary, IVL of the B-, T- and NK-cell phenotypes is clinicopathologically distinct and shows similarities to their more common counterparts, i.e. diffuse large B-cell lymphoma, peripheral T-cell lymphoma, unspecified and extranodal NK/T-cell lymphoma, nasal type.     

Angioimmunoblastic T-cell lymphoma complicated with EBV-associated B-cell lymphoma

A 71-year-old man with high fever and enlargement of the bilateral submandibular, cervical and inguinal lymph nodes was hospitalized at Hiroshima University Hospital. The immunohistochemical and pathologic findings from the biopsy specimens led to the diagnosis of angioimmunoblastic T-cell lymphoma (AILT) with a cluster of CD20-positive cells. Flow cytometry analysis by two-color staining did not reveal any neoplastic B cells. Southern blot analysis showed rearrangement of both the IgH gene and the TCR gene. Furthermore, PCR of the IgH gene using DNA extracted from purified CD19-positive cells from the lymph nodes showed a monoclonal band, and it was different from that of purified CD138-positive cells from the bone marrow. Furthermore, monoclonal Epstein-Barr virus (EBV) infection was detected with PCR using the SL18 and SL19 primers of the LMP-1 gene. Numerous EBER-positive cells were detected diffusely in the lymph nodes. These findings indicated a diagnosis of angioimmunoblastic T-cell lymphoma complicated with EBV-associated B-cell lymphoma, and that immunodeficiency in AILT led to an expansion of EBV infected B-cells.     

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

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.