Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes > 200 × 10/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19, CD20, HLA-DR, CD22, CD5, Kappa, CD25, CD71, Lambda, CD7, CD10, CD23, CD34, CD33, CD13, CD14, CD117, CD64, CD103, and CD11c. The karyotype showed complex abnormality: 46XX,+ 3,-10, t(8;14)(q24; q32)[11]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.
Aged ; B-Lymphocytes ; pathology ; Female ; Humans ; Immunophenotyping ; Lymphoproliferative Disorders ; genetics ; pathology ; Translocation, Genetic

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.
Classification ; Cytogenetics ; Diagnosis ; In Situ Hybridization, Fluorescence ; Lymphoma ; Lymphoma, B-Cell ; Lymphoproliferative Disorders* ; Molecular Biology ; Pathology, Molecular ; T-Lymphocytes ; World Health Organization

Central Nervous System ; pathology ; Humans ; Lymphoproliferative Disorders ; pathology ; Transplantation ; adverse effects

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders.
B-Lymphocytes/*pathology/*virology ; Diagnosis, Differential ; Disease Management ; Epstein-Barr Virus Infections/*complications ; Herpesvirus 4, Human/*physiology ; Humans ; Lymphoproliferative Disorders/*diagnosis/*etiology/therapy

Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.
Cell Transformation, Viral ; Epstein-Barr Virus Infections/*complications ; Herpesvirus 4, Human/*physiology ; Humans ; Killer Cells, Natural/immunology/metabolism/*pathology/*virology ; Lymphoproliferative Disorders/diagnosis/*etiology/therapy ; T-Lymphocytes/immunology/metabolism/*pathology/*virology

The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein-Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described.
Animals ; Disease Models, Animal ; Epstein-Barr Virus Infections/complications/immunology/*virology ; Herpesvirus 4, Human/*physiology ; Heterografts ; Humans ; Killer Cells, Natural/pathology/virology ; Lymphoproliferative Disorders/etiology ; Mice ; Mice, SCID ; T-Lymphocytes/pathology/virology

Castleman's disease (CD) is a rare lymphoproliferative disorder that can involve single or multiple lymph nodes in the body. Especially, the localized form of CD is known to be well-controlled by using a surgical resection. On occasion, the surgeon may confront an abdominal and retroperitoneal mass of unknown origin. Thus, we present this case in which we treated a 16-year-old female patient for CD and investigated how to evaluate and manage the situation from the standpoint of CD. Also, we give a review of the pathology, clinical manifestation, diagnosis, and treatment of CD.
Abdomen* ; Adolescent ; Diagnosis ; Female ; Giant Lymph Node Hyperplasia* ; Humans ; Lymph Nodes ; Lymphoproliferative Disorders ; Pathology, Clinical

Cutaneous pseudolymphoma is an uncommon, benign lymphoproliferative disorder of the skin. Although this condition is most commonly idiopathic, its occurrence has been associated with cosmetic tattoos. We report a unique case of cutaneous pseudolymphoma that occured after accidental, traumatic inoculation of a red pigment in a healthy 33-year-old woman.
Adult ; Betamethasone ; analogs & derivatives ; therapeutic use ; Biopsy ; Coloring Agents ; adverse effects ; Female ; Forehead ; pathology ; Humans ; Lacerations ; Lymphoproliferative Disorders ; diagnosis ; etiology ; Pseudolymphoma ; chemically induced ; diagnosis ; Skin ; pathology ; Skin Diseases ; chemically induced ; diagnosis ; Triamcinolone Acetonide ; therapeutic use

The aim of this study was to analyze the clinical features and laboratory findings of adult Epstein-Barr virus associated T/NK cell lymphoproliferative disease (EBV+T/NK-LPD) and to investigate the early diagnosis and prognosis of EBV+T/NK-LPD. The clinical data of 19 adult patients with EBV+T/NK-LPD were retrospectively analyzed. The results indicated that there were 11 males and 8 females. The median age was 32 years (range: 20-70 years). The average duration from onset of symptoms to diagnosis was 3.5 months. The median survival time was 2.5 months. Unkown fever, hepatosplenomegaly, liver dysfunction and interstitial pneumonia were the main clinical features. High levels of β2-MG, LDH, TNF, IL-6 and significantly increased EBV-DNA level (median level > 10(6) copies/ml) were occurred in all the patients. Cytopenia was seen in 18 cases. Morphologically, atypical large granular lymphocytes and hemophagocytosis were common in bone marrow smears. Deletion of CD5 or CD7 were frequently observed in T/NK lymphocytes in bone marrow cells by flow cytometry. Bone marrow biopsy showed atypical lymphocyte interstitial infiltrated in 10 cases, while a few large cells infiltrated in 6 cases. Immunohistochemistry showed the expression of CD3(+)CD56(+) were seen in 2 cases, CD3(+)CD8(+) in 11 cases and CD3(+)CD4(+) in 3 cases. TIA-1 and EBER were positive in all biopsy specimens. Three cases underwent biopsy of lymph nodes showed reactive proliferations of lymphocytes. All the patients died of multiorgan failure. It is concluded that the fever, hepatosplenomegaly are the most common clinical features in adult EBV+T/NK-LPD, the bone marrow infiltration of EBV-infected T/NK lymphocytes and significantly increased EBV-DNA level can be observed in all cases, the clinical outcome of this disease is poor, these clinical and experimental features can be served as a reliable marker for the timely diagnosis of adult EBV+T/NK-LPD.
Adult ; Aged ; Epstein-Barr Virus Infections ; pathology ; Female ; Humans ; Immunophenotyping ; Killer Cells, Natural ; virology ; Lymphoproliferative Disorders ; pathology ; virology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes ; virology ; Young Adult

OBJECTIVETo analyze the prevalence of Epstein Barr Virus (EBV) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSWe retrospectively analyzed the clinical characteristics of 720 patients received allo-HSCT from January 2010 through December 2011 in the Stem Cell Transplant Center of People's Hospital.

RESULTSOf 720 patients (469 male presented and 251 females), with a median age of 30 years (range, 2 to 67 years) old, 66 patients were presented with EBV reactivation. The cumulative incidence of EBV reactivation was (9.3±1.1)%, with a median days of 54.5 (range, 18 to 253 days). During one- year post-transplantation, the cumulative incidences of EBV reactivation in sibling allo-HSCT, haploidentical HSCT and unrelated donor HSCT were (1.3±0.7)%, (13.7±1.7)%, and (9.1±4.4)%, respectively. In patients with haplo-identical HSCT, the cumulative incidences of EBV viremia, probable EBV disease, and post-transplant lymphoproliferative disease (PTLD) were (5.8±1.1)%, (5.7±1.1)%, and (2.3±0.7)%. The mortality was (33.9±5.9)% in all patients with EBV infection: (63.6±15.8)% in PTLD, (42.3±9.9)% in probable EBV disease, (13.8±6.5)% in EBV viremia. By univariate and multivariate analysis, the use of ATG was an independent risk factor for EBV infection.

CONCLUSIONEBV reactivation is a common complication in patients with allo- HSCT, especially high mortality in PTLD and probable EBV disease. The use of ATG was an independent risk factor for EBV infection.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Epstein-Barr Virus Infections ; pathology ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Herpesvirus 4, Human ; Humans ; Lymphoproliferative Disorders ; virology ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Transplantation, Homologous ; Virus Activation ; Young Adult