Angiotropic (intravascular) large cell lymphoma of T-cell phenotype presenting as acute appendicitis in a patient with acquired immunodeficiency syndrome.

We describe a patient with acquired immunodeficiency syndrome who presented with acute appendicitis but was found to have angiotropic large cell lymphoma (ALCL) by pathologic examination of the appendectomy specimen, without acute inflammation. Very rare cases of angiotropic large cell lymphoma have been reported in patients with human immunodeficiency virus infection, and most cases of this rare lymphoma are of B-cell origin, but in this instance immunohistochemical analysis showed a T-cell phenotype.     

Systemic lymphoma arising from hydroa vacciniforme-like lymphoma: report of two cases with review of literature

Hydroa vacciniforme-like lymphoma (HVLL) is an extremely rare lymphoma described in children that occurs mainly in Asia and Latin American countries. It is an Epstein-Barr virus (EBV)-positive lymphoproliferative disease (LPD) characterized by a monoclonal proliferation of T or NK cells. In this study, we report the clinical and pathological features of two Chinese patients with HVLL showed T-cell phenotype expressing CD4. The two patients generally presented with similar clinical histories of waxing and waning ulcerative blistering lesions for ten years or more until progression to systemic lymphoma. One patient died two months after progression and another is alive with disease. In the two cases, persistence infection of EBV may be attributed to the disease progression, and systemic lymphoma arising from HVLL behaves in an aggressive fashion and is predisposing to chemotherapeutic agent resistance.     

Epstein-Barr virus-associated extranodal NK/T-cell lymphoma, nasal type of the hypopharynx, in a renal allograft recipient: case report and review of literature.

Posttransplant lymphoproliferative disorders (PTLPDs) are predominantly B-cell lymphoproliferations, whereas a T-cell origin is rarely observed. In contrast to B-cell PTLPD, T-cell PTLPDs show an inconsistent association with Epstein-Barr virus (EBV). Until now, only 13 cases of EBV-associated T-cell PTLPDs have been reported. We describe a case of an EBV-associated T-cell PTLPD in a renal allograft recipient 2 years after transplantation. Histologic examination showed medium- to large-sized lymphoid cells with an angiocentric growth pattern and necrosis. The atypical cells showed a CD2+, CD3epsilon+, CD7+, CD43+, CD45R0+, CD56+, and CD4-, CD5-, CD8- betaF1- phenotype with expression of the latent membrane protein (LMP)-1 of EBV. In addition, EBV-specific RNAs (EBER 1/2) were identified by in situ hybridization. Molecular analysis of the T-cell receptor (TCR) gamma chain by polymerase chain reaction (PCR) showed a polyclonal pattern. The morphologic, immunohistochemical, and molecular findings were consistent with a diagnosis of an EBV-associated extranodal natural killer (NK)/T-cell non-Hodgkin lymphoma (NHL) of nasal type. To our knowledge, this is the first reported case of this rare entity in the posttransplant setting.     

Cutaneous intravascular natural killer/T cell lymphoma with peculiar immunophenotype

Intravascular lymphoma (IVL) is a rare entity. Most cases are a variant of extranodal diffuse large B cell lymphoma, and fewer than 10% of the published cases are of T cell origin. Only intravascular B cell lymphoma is recognized as a distinct entity in the most recent World Health Organization (WHO) classification of lymphoproliferative disorders. We describe a case of cutaneous natural killer (NK)/T IVL, with a cytotoxic immunophenotype and Epstein–Barr virus (EBV) positivity. However, our case was immunohistochemically negative not only for T cell receptor (TCR)‐βF1 and TCR‐γ (TCR‐silent), but also for CD56, making it the first triple‐negative NK/T IVL case to be described. We urge recognition of this NK/T cell lineage intravascular lymphoma due to its particular immunophenotypical profile and its unvarying relationship with EBV. Its occurrence should not be considered a coincidence, but rather a key aspect of the pathogenic background of this haematological neoplasm.     

Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient

The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity.     

A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin''s lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas.

This study analyzes the association of Epstein-Barr virus (EBV) with non-Hodgkin's lymphoma (NHL) arising in patients without pre-existing overt immunodeficiency. The authors examined 201 lymphomas (105 high-grade B-cell, 82 peripheral T-cell, 7 high-grade non-B-cell, non-T-cell, and 7 hairy-cell leukemia) for EBV gene expression by immunohistologic procedures using monoclonal antibodies to EBV latent, immediate early, and replicative infection antigens. Transformation-associated EBV latent membrane protein 1 (LMP 1) was detected in 13 (6%) NHL, comprising 4 (4%) high-grade B-cell, 8 (10%) peripheral T-cell, and 1 non-B-cell, non-T-cell lymphomas. Anaplastic large-cell lymphoma of T-cell type was consistently LMP 1-negative. EBV nuclear antigen 2 was demonstrated in only three (1%) cases. Induction of replication as defined by expression of the immediate early BamHI Z leftward reading frame 1 (BZLF1) protein was detected in five cases, but early (EA) and late (VCA and MA) lytic cycle antigens were only found in two cases and in one case, respectively. The presence of EBV was confirmed by in situ DNA hybridization in 9 of 11 EBV antigen-positive lymphomas. This study shows the surprisingly frequent presence of EBV in peripheral T-cell NHL in European patients without pre-existing overt immunodeficiency. Interestingly, most sporadic B-cell NHL are not associated with the virus. Furthermore, the usefulness of selected monoclonal antibodies for the routine immunohistological diagnosis of EBV infection was confirmed.     

Newly developed multiple myeloma in a patient with primary T-cell lymphoma of bone

Primary non-Hodgkin's lymphoma of bone (PLB) is rare, and generally presents as a single extensive and destructive bone lesion. Histopathologically, most cases present as diffuse large B-cell lymphoma, and T-cell lymphoma is rare. By contrast, multiple myeloma is a disease defined as the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. We report a case of multiple myeloma that developed during treatment of PLB in a type of T-cell. A 48-yr-old man was diagnosed as T-cell PLB, stage IE, 18 months ago. The patient received the chemoradiotherapy and salvage chemotherapy for PLB. However, the lymphoma progressed with generalized bone pain, and laboratory findings showed bicytopenia and acute renal failure. On bone marrow biopsy, the patient was diagnosed as having multiple myeloma newly developed with primary T-cell lymphoma of bone. In spite of chemotherapy, the patient died of renal failure.     

Nasal CD56 positive small round cell tumors

CD56-positive nasal and nasal-type natural killer (NK)/T-cell lymphoma is now a well-defined disease entity. Rare cases of blastic NK-cell lymphoma positive for CD56 have been recently reported. However, CD56 expression is also identified in several types of non-hematopoietic small round cell tumors in which lymphoma is included as a differential consideration. Here, we present nine cases of CD56+ small round cell tumors of histological origin unrelated to nasal NK/T-cell lymphoma. Eight of the nine cases presented as solid tumors of the sinonasal region. Clinical, histological, ultrastructural, and immunohistochemical examination and gene analysis for T-cell receptor (TcR) and immunoglobulin heavy chain (IgH) genes and in situ hybridization (ISH) for Epstein-Barr virus (EBV) were performed. Two cases presented with features consistent with blastic NK-cell lymphoma or lymphoblastic lymphoma of NK-cell phenotype. These cases showed features of lymphoblastic lymphoma, phenotypes of sCD3-, cCD3+, CD45+, CD56+, TdT+, and human leukocyte antigen (HLA)-DR+, germline of IgH and TcR genes, and EBV negative reactivity. One case had myeloid/NK-precursor acute leukemia/lymphoma with a phenotype of CD13+, CD33+, CD34+, CD56+, and MPO-. Three cases were neurogenic, including one case of olfactory neuroblastoma and two of primitive neuroectodermal tumors (PNET). It was difficult to differentiate CD56+ PNET from blastic NK-cell lymphoma, especially when only paraffin-embedded sections were available. Myogenic markers, such as HHF35, alpha-sarcomeric actin, and desmin, were positive in three cases of rhabdomyosarcomas. Our findings suggest that as CD56 is used more routinely as a marker in immunohistochemical staining, the differential diagnosis of extranodal lymphohematological malignancies and small round cell tumors will become more complicated.     

Epstein–Barr virus in Reed–Sternberg G-like cells in non Hodgkin's lymphomas

In the course of our study on Hodgkin's disease (HD), ten cases of non-Hodgkin's lymphomas (NHL) containing Hodgkin and Reed-Sternberg-like (MRS) cells were encountered. Many of these cases had initially been diagnosed as HD, but on careful review of the histology, with the aid of immunophenotyping studies, they were reclassified as NHL. The presence of Epstein–Barr virus (EBV) in these HRS-like cells was investigated using a combination of EBER in situ hybridization (ISH) and immunostaining for the detection of EBV-encoded latent membrane protein (LMP). HRS-like cells in four cases (two lymphoplasmacytoid lymphomas, one Richter's transformation of lymphoplasmacytoid lymphoma, and one immunoblastic lymphoma of T-cell type) were found to be EBV-positive. In two of these cases, a second biopsy taken up to 10 years later also contained EBV in the HRS-like cells. In three of the four cases, HRS-like cells expressed the activation antigen CD30, but the expression of B- or T-cell antigens was variable. All cases of T-cell-rich B-cell lymphomas were negative for EBV. In conclusion, EBV may play a role in the development of HRS-like cells i some cases of NHL. The relationship of HRS-like cells to HRS cells of HD is discussed.     

Methotrexate-associated lymphoproliferative disorders mimicking angioimmunoblastic T-cell lymphoma

Patients affected by autoimmune diseases (rheumatoid arthritis (RA), psoriasis, and dermatomyositis) treated with methotrexate (MTX) develop lymphoproliferative disorders (LPDs). These cases have been reported to be diffuse large B-cell lymphoma, Hodgkin lymphoma, or polymorphous post-transplant LPDs. However, angioimmunoblastic T-cell lymphoma (AITL) is extremely rare in the medical literature. In this report, we describe three cases of RA patients who developed MTX-associated LPDs resembling AITL. They developed systemic lymph node swelling after initiation of MTX. The affected lymph nodes showed the histological finding of AITL: polymorphous infiltrates, mainly T-cells and arborizing high endothelial venules. Two cases showed a predominance of CD4-positive cells in proliferative T-cells, whereas the third case showed CD8-positive cells. CD10 was negative in all cases. RNA in situ hybridization of Epstein-Barr virus (EBV) demonstrated EBV-positive B-cells to be scattered in two cases, but not in one case. The lymphoadenopathy spontaneously regressed with cessation of MTX in all three cases, but one case recurred. These are interesting cases of MTX-associated LPDs mimicking AITL, and cessation of MTX is the only cure for patients with MTX-associated LPDs resembling AITL.     

Fulminant EBV-driven CD8 T-cell lymphoproliferative disorder following primary acute EBV infection: a unique spectrum of T-cell malignancy

Fulminant Epstein-Barr virus (EBV)-driven clonal T-cell lymphoproliferative disorder (T-LPD) is rare and most patients are of Asian origin. The disease usually develops shortly after primary acute EBV infection and the mechanism remains poorly understood. Here we report such a rare case in a 28-year-old Caucasian female with systemic lupus erythematosus (SLE). Immunophenotypic and molecular studies revealed that the proliferating lymphoid cells displayed a CD8(+) T-cell phenotype with clonal rearrangement of the T-cell receptor gamma gene. Epstein-Barr virus-encoded RNA was also observed in the clonal lymphoid cells by in situ hybridization. The patient subsequently developed fatal virus-associated hemophagocytic syndrome one month after the primary acute EBV infection. The case represents the first report of fulminant EBV-driven CD8(+) T-LPD occurring in an immunocompromised Caucasian SLE patient. This study, along with studies of similar Asian cases reported in the literature, suggests that dysregulated immunity due to either acquired or genetically determined susceptibility may result in an abnormal response to primary EBV infection and contribute to the pathogenesis of EBV-mediated fatal T-LPD.     

Burkitt lymphoma with unusual granulomatous reaction. A case report

Formation of epithelioid histiocytic cell granulomas has been described in the post in various neoplasms, hematologic malignancies included. Among lymphoproliferative disorders such changes are commonly found in Hodgkin lymphoma and T-cell non-Hodgkin lymphomas (NHL), but are rarely described in B-NHL, like Burkitt lymphoma. This report presents a case of sporadic Burkitt lymphoma accompanied by a sarcoid-like reaction without any clinical, laboratory or histological evidence of microorganisms nor sarcoidosis. Using in situ hybridization and polymerase chain reaction the presence of the Epstein-Barr virus (EBV) was detected in the analyzed lymphoma cells. EBV demonstrated latency I phenotype as defined by the lack of immunohistochemical positivity of latent membrane protein 1 (LMP1). Cytogenetic investigation using fluorescence in situ hybridization uncovered c-MYC mutation and provided indirect indication for the MYC/IgL fusion gene. The lack of EBV positivity in histiocytes indicated the reactive character of the granulomatous reaction in relation to the neoplasm. The role of the granulomatous reaction in the biology and prognosis of Burkitt lymphoma and the function of EBV infection in its development remain to be established.     

EBV-associated B- and T-cell posttransplant lymphoproliferative disorders following primary EBV infection in a kidney transplant recipient

Posttransplant lymphoproliferative disorders (PTLDs) usually are of B-cell lineage and associated with Epstein-Barr virus (EBV). PTLDs of T-cell lineage are much less common and infrequently associated with EBV. We report a rare case of a girl in whom B-cell and T-cell PTLDs developed following 2 EBV-negative kidney transplants. Within 2 years of the second transplantation, the originally EBV-negative patient developed both an EBV-associated clonal B-cell PTLD involving lymph nodes and an EBV-positive T-cell PTLD involving bone marrow and liver. These proliferations occurred concurrently with evidence of primary EBV infection and high plasma viral load. The patient eventually died of multiorgan failure 5 years after the initial transplant (3 years after the second transplant). To our knowledge, only 4 cases of both B-cell and T-cell PTLDs have been reported. Only 2 cases have been proven to be monoclonal and EBV-associated, as in this case, the first following kidney transplantation.     

Nasal natural killer lymphoma associated with Epstein-Barr virus in a patient infected with human immunodeficiency virus

Nasal natural killer (NK) lymphoma associated with Epstein-Barr virus (EBV) is a rare lymphoma that has not yet been reported in patients with human immunodeficiency virus (HIV). This report describes the first case, to our knowledge, of nasal NK cell lymphoma in an HIV-positive patient. A 50-year-old African man presented with an obstructive nasopharyngeal tumor, leading to the diagnosis of HIV infection. Nasal biopsy specimens showed NK cell lymphoma, confirmed on nasal tissues by morphologic, immunohistochemical, and polymerase chain reaction studies using a denaturing gradient gel electrophoresis technique that showed no T-cell receptor gamma rearrangement. The EBV was detected by in situ hybridization. The patient received chemotherapy but died from infection. To our knowledge, this is the first reported case of nasal NK cell lymphoma associated with EBV in an HIV patient. Involvement of EBV in HIV non-B-cell lymphomas may represent a further manifestation of opportunistic EBV infection arising in these patients.     

EBV in situ hybridization study for non-Hodgkin's lymphomas.

Epstein-Barr virus(EBV) has been implicated in the pathogenesis of B-lymphoproliferative disorders, T-cell lymphomas and Hodgkin''s disease. In this report, we performed an in situ hybridization study on EBV genome in 10 cases of nasal non-Hodgkin''s lymphoma(NHL), 20 cases of Waldeyer''s ring(WR) NHL, and 20 cases of nodal NHLs to document EBV association with lymphomas in Koreans. For immunophenotyping, monoclonal antibodies for CD 20, MB 2, CD 45Ro & CD 43 were used. For in situ hybridization study, EBV DNA probe for Bam HI ''V'' fragment and EBV RNA probe for EBER and BHLF were used. Twenty two cases(44%) of malignant lymphomas were positive for EBV genome. Generally, T-cell lymphomas showed a higher positive rate(61%) than B-cell lymphomas(24%). Among T-cell lymphomas, nasal lymphomas showed a higher positive rate(80%) than WR(50%) or nodal lymphomas(50%). Of 22 EBV genome positive cases, 10 cases were positive for EBER, 10 cases for BHLF, and 2 cases for both EBER and BHLF. The histologic types by Working Formulation(WF) were not correlated with EBV genome positive rate, whereas lymphomas showing the histologic spectrum of polymorphic reticulosis(PR) showed a higher positive rate(65%) than lymphomas without PR-like features(40%). These results indicate that nasal T-cell lymphomas with the histologic spectrum of PR are strongly associated with EBV and that the anatomic site may be an important factor in this association.     

Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria

The frequency of Epstein-Barr virus (EBV) in anaplastic large cell lymphoma (ALCL) has been controversial. The interpretation of previous studies is complicated by the use of nonuniform EBV detection methods and the inclusion of cases of CD30-positive diffuse large B-cell lymphoma and so-called "ALCL, Hodgkin-like," as defined in the Revised European-American Lymphoma classification scheme. In the current World Health Organization (WHO) classification system, both of these tumors are excluded from the ALCL category. Also, recently developed antibodies (eg, the antibody specific for PAX-5/B-cell-specific activator protein [BSAP]) provide new, sensitive tools for identifying neoplasms of B-cell lineage that can morphologically resemble ALCL. In this study we evaluated 64 cases of ALCL of T- or null-cell lineage, defined according to the WHO classification system, for the presence of EBV. All tumors were negative for B-cell antigens, including PAX-5/BSAP and CD20 or CD79a. The study group included 27 (42%) anaplastic lymphoma kinase (ALK)-positive (18 T-cell and 9 null-cell) and 37 (58%) ALK-negative (30 T-cell and 7 null-cell) tumors analyzed by in situ hybridization for EBV-encoded RNA (EBER) or immunohistochemistry for EBV-latent membrane protein type 1. All 64 cases were negative for EBV. We conclude, based on the current definition of ALCL in the WHO classification, there is no role for EBV in ALCL arising in Western patients. We suggest that published reports of EBV in a small proportion of ALCL cases in Western patients can be explained by the inclusion of tumors no longer considered to be in the current classification of ALCL, such as CD30-positive anaplastic tumors of B-cell origin.     

Pyothorax-associated lymphoma: a case showing transition from T-cell-rich polymorphic lesion to diffuse large B-cell lymphoma

Pyothorax-associated lymphoma was found in a man who had a history of collapse therapy for pulmonary tuberculosis about 50 years ago. An autopsy specimen revealed histology of diffuse large B-cell lymphoma with latency III Epstein-Barr virus (EBV) infection. However, an open biopsy 2 years and 7 months before death showed a polymorphic appearance with abundant T-lymphocytes. Most of the EBV-infected atypical lymphocytes did not express either B- or T-cell markers as far as examined in the paraffin-embedded biopsy specimen, and rearrangements of immunoglobulin and T-cell receptors were not found. It seemed difficult to diagnose a B-cell lymphoma at the time of biopsy. However, retrospectively considered, if a phenotype of EBV-infected atypical lymphocytes is uncertain in cases showing polymorphic appearance, it might be better to consider the future evolution to overt B-cell lymphoma. Since pyothorax-associated lymphoma shows latency III infection of EBV, at least the immunohistochemistry of EBNA-2 and LMP-1 seems helpful for the diagnosis to prove which cells are infected by EBV.     

Systemic EBV+ T-cell lymphoma in elderly patients: comparison with children and young adult patients

Fulminant Epstein-Barr virus (EBV+) T-cell lymphoma in immunocompetent elderly patients is rare and its character has not been well defined. This study analyzed the clinicopathological features of five elderly patients (group A: 50-84 years) and compared them with those of eight children and young adult patients with systemic T-cell lymphomas (group B: 10-34 years). Group A more commonly presented with generalized lymphadenopathy (n = 3) than did group B (n = 1). Chronic active EBV infection (n = 3) and hydroa vacciniforme-like eruptions (n = 1) were seen in group B, while group A showed no evidence of chronic EBV infection, but did show chronic hepatitis B or C virus infections (n = 3). The histological and immunophenotypical findings were similar. All patients died within 1 to 14 months of diagnosis. These findings suggest that EBV+ T-cell lymphoma in elderly patients is a unique disease with an underlying derangement of T-cell immunity and failure to eradicate infected virus. Additional factors related to senility may play a role in the disruption of homeostasis between the virus and the host's immune system.     

非霍奇金淋巴瘤EB病毒特异DNA序列的检测

目的　探讨EB病毒 (EBV)与中国南方地区非霍奇金淋巴瘤 (NHL)的相关性 ,以及EBV与不同类型NHL的关系。方法　采用PCR技术 ,检测 2 0 6例石蜡包埋的NHL组织及 2 3例反应性增生的淋巴组织中的EBV特异DNA序列。结果　(1 ) 2 0 6例NHL组织中 ,94例PCR扩增出EBV特异的DNA序列 ,阳性率 4 5 6 % ;对照组反应性增生的淋巴组织 2 3例中 ,5例阳性 ,阳性率 2 1 7% ;两者差异有显著性 (P <0 0 5 )。 (2 ) 2 0 6例NHL中B NHL 1 2 8例 ,EBV阳性者 4 8例 ,阳性率 37 5 % ;T NHL 78例 ,EBV阳性者 4 6例 ,阳性率 5 9 0 %。两者差异有显著性 (P <0 0 5 )。结论　EBV与中国南方地区NHL ,特别是T NHL有一定的相关性