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Development of Epstein-Barr virus-associated lymphoproliferative disorder and hemophagocytic lymphohistiocytosis during long-term lenalidomide maintenance therapy in multiple myeloma.

Reactivation of Epstein-Barr virus (EBV) has been considered a very rare event among patients on immunomodulatory drugs (IMiDs) such as lenalidomide, and an association between the two has not well been recognized. We have recently experienced a rare case of multiple myeloma in which the patient had suffered EBV reactivation during long-term lenalidomide maintenance therapy. The patient subsequently developed EBV-associated lymphoproliferative disease (LPD) as well as EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which was fatal despite intensive treatment. Although rare, clinic

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… Natkunam Y Gratzinger D Chadburn A Goodlad JR Chan JKC Said J Immunodeficiency-associated lymphoproliferative disorders: time for reappraisal? Blood 2018 132 18 1871 1878 10.1182/blood-2018-04-842559 30082493 PMC6213318 11. … Pina-Oviedo S Miranda RN Jeffrey L Medeiros M Cancer therapy-associated lymphoproliferative disorders: an under-recognized type of immunodeficiency-associated lymphoproliferative disorder Am J Surg Pathol 2018 42 1 116 129 10.1097/PAS.0000000000000954 29112013 12. …

Cyclin D1 expression, cell proliferation, and clonal persistence characterize primary cutaneous CD4+ small or medium T-cell lymphoproliferative disorder.

AIMS: The aim was to gain insight into the biology of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD). METHODS: We describe the histopathological and clinical characteristics of 177 PCSM-LPD diagnosed at our consultation centre. We performed immunohistochemical multistaining in a subset of cases (n = 46) including PD1, Cyclin D1, and multiple markers of proliferation. We evaluated clonal T-cell-receptor-(TCR) rearrangements and used tissue microdissection to analyse TCR-clonality of PD1(+) cells. RESULTS: The cohort of n = 177 PCSM-LPD included 84 males and

A Rare Case of Monomorphic T-Cell Posttransplant Lymphoproliferative Disorder Presenting as Primary Cutaneous Anaplastic Large Cell Lymphoma, ALK Negative.

Posttransplant lymphoproliferative disorders are a serious complication of hematopoietic and solid organ transplants secondary to iatrogenic immunosuppression. Most cases present as B-cell proliferations which are often Epstein-Barr virus positive; however, ∼10% of cases are T/NK cell and are less commonly associated with Epstein-Barr virus. Of these, cutaneous T/NK-cell lymphomas are exceedingly rare. We report a case of a 69-year-old male, liver transplant recipient who presented with a tender, bright red papule on the left arm during his annual skin cancer screening. Histopathologic evaluat…

Successful treatment with rituximab for central nervous system vasculitis caused by Epstein-Barr virus-associated lymphoproliferative disorder with immunoglobulin M gammopathy.

Monoclonal gammopathy of undetermined significance (MGUS) is associated with several autoimmune conditions, including central nervous system (CNS) vasculitis. Epstein-Barr virus (EBV) is a pathogen capable of triggering a systemic immune response and is involved in the occurrence of a wide range of B-cell lymphoproliferative disorders. In systemic autoimmune diseases, EBV infection is suspected to play a central role in pathogenesis. Here, we present a case that was thought to be a systemic autoimmune disease and CNS vasculitis that developed after EBV infection, demonstrating that rituximab i…

Clinicopathological analysis of primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder: a retrospective study of 22 patients.

BACKGROUND: Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder has been defined as a type of lymphoproliferative disorder with indolent clinical course and excellent prognosis, yet a precise diagnosis is still hard to reach. METHODS: A retrospective analysis of 22 patients including 16 females and six males was performed. RESULTS: The age of patients ranged from 5 to 79 years. The average age of all patients was 43.5, and the median age of all patients was 44.5. Two patients had multiple lesions, and others were presented with a solitary asymptomatic

Hepatic Hodgkin Lymphoma Presenting as Solitary Hepatic Mass Following Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorder in a Patient With Rheumatoid Arthritis.

Lymphoproliferative disorders (LPDs) occur frequently in patients with rheumatoid arthritis (RA) under methotrexate treatment. Some LPDs spontaneously regressed after methotrexate discontinuation, but classic Hodgkin lymphoma (CHL)-type LPDs frequently relapse, and chemotherapy is usually required for the treatment. CHL usually spreads in contiguous lymph nodes and then infiltrates in organs at an advanced stage. Thus, hepatic Hodgkin lymphoma (HHL) without lymphadenopathy is extremely rare at diagnosis. We present a case of methotrexate-associated LPDs associated with systemic lymphadenopathy…

Post-transplant Lymphoproliferative Disorder in Recipient's Reconstructed Middle Hepatic Vein After Pediatric Living Donor Liver Transplant: A Case Report.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is known as one of the most frequent post-transplant neoplastic diseases, which may lead to recipient and graft morbidity after liver transplant. PATIENT: A 14-year-old boy received pediatric living donor liver transplant (right living graft) 29 months ago, with etiology of biliary atresia. During 22-month follow-up after transplant, computed tomography and positron emission tomography with computed tomography scan showed a single progressive mass locating in the graft cutting surface with occlusive reconstructed middle hepatic v

Early Onset Post-transplant Lymphoproliferative Disorder Presenting with Diarrhea Post-orthotopic Liver Transplant Treated Successfully with Single Rituximab Agent.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication seen in hematologic stem cell (HSC) and solid organ transplantation that results from immune suppressant medications needed to prevent allograft rejection. Epstein-Barr virus (EBV) has been implicated in a majority of these cases, specifically with B-cell-predominant lymphomas. We present a 57-year-old female who underwent an orthotopic liver transplant and presented with diarrhea and weight loss. At the time of transplantation, the patient's quantitative EBV titers were negative; however, repeat titers during her admis

Diagnosis and treatment of neoplastic post-transplant lymphoproliferative disorder following hematopoietic stem cell transplant in β-thalassemia: A pediatric case report.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is the most common form of lymphoproliferation in childhood and is associated with significant morbidity and mortality. In this report we reviewed the case of a pediatric patient who experienced PTLD after allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling. METHODS: The clinical characteristics, diagnosis, and treatment of PTLD after sibling HSCT in a 4-year-old boy with severe β-thalassemia was retrospectively reviewed. RESULTS: Medical records revealed the patient

Post-transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: report of two cases and literature review.

Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of

Absence of the V617F JAK2 mutation in the lymphoid compartment in a patient with essential thrombocythemia and B-chronic lymphocytic leukemia and in two relatives with lymphoproliferative disorders.

BACKGROUND: Myeloproliferative neoplasms likely involve both myeloid and lymphoid lineages. Nevertheless, the coincidence of chronic myeloproliferative and lymphoproliferative diseases in the same patient is a rare phenomenon. METHODS: We report a case of a patient having essential thrombocythemia (ET) and B-chronic lymphocytic leukemia (B-CLL). In this patient and in 2 relatives with lymphoproliferative disorders, we searched for JAK2(V617F) mutation in lymphocytes. RESULTS: In the patient with ET and B-CLL, we identified homozygous JAK2(V617F) mutation in the granulocytic compartment. Both…

Prior immunosuppressive therapy with antithymocyte globulin increases the risk of EBV-related lymphoproliferative disorder following allo-SCT for acquired aplastic anaemia.

We reviewed the incidence and risk factors for EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD) in 89 patients with acquired aplastic anaemia (AAA) receiving allogeneic transplants between 1989 and 2006. The overall incidence of EBV-PTLD was 6.3% (5/89) with no cases in those receiving an allograft for constitutional BM failure syndromes (n=30) during the same period. There was no impact of age, gender, donor status, CMV seropositivity, GVHD and graft cell dose on the occurrence of PTLD. Although both reduced intensity conditioning (RIC) and the prior use of antithymocyte gl

Plasmacytic hyperplasia--the early form of posttransplant lymphoproliferative disorder--with atypical morphology and clinical course in patient after liver transplantation: a case report.

This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)--plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr vi

Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor f…

Serotype-dependent recombinant adeno-associated vector (AAV) infection of Epstein-Barr virus-positive B-cells, towards recombinant AAV-based therapy of focal EBV + lymphoproliferative disorders.

BACKGROUND: B-cell proliferative disorders, such as post-transplant lymphoproliferative disease (PTLD), are increased among persons afflicte … candidate vector for the development of rAAV-based oncolytic therapy targeting focal EBV-bearing B-lymphoproliferative disorders.

Hyperplasia of hair follicles and other adnexal structures in cutaneous lymphoproliferative disorders: a study of 53 cases, including so-called pseudolymphomatous folliculitis and overt lymphomas.

We studied 53 cutaneous lymphoproliferative disorders, all of which manifested hair follicle hyperplasia. There were 42 cases conforming to the description of pseudolymphomatous folliculitis (PLF) and 11 cases of authentic lymphomas including mycosis fungoides, CD30+ anaplastic large cell lymphoma, diffuse large B-cell lymphoma, B-cell small cell lymphoma/leukemia, and peripheral T-cell lymphoma, not otherwise specified. All patients with PLF clinically presented with a solitary nodule preferentially involving the face. Beside hair follicle hyperplasia, the typical features were a dense infilt…

Oligoclonal T cell expansions in pulmonary lymphoproliferative disorders: demonstration of the frequent occurrence of oligoclonal T cells in human immunodeficiency virus-related lymphoid interstitial pneumonia.

We used a denaturing gradient gel electrophoresis (DGGE) procedure with 40-nucleotide guanine- and cytosine-rich sequences in the polymerase chain reaction (PCR) and sequencing analysis to analyze the T cell antigen receptor (TCR)-Vgamma gene repertoire of infiltrating T lymphocytes in pulmonary lymphoproliferative disorders. Six of 15 low-grade mucosa-associated lymphoid tissue (MALT) lymphomas and 8 of 15 cases of lymphocytic interstitial pneumonia (LIP) showed some oligoclonal bands for TCR-Vgamma genes on DGGE. Sequencing analysis demonstrated plural oligoclonal TCR-Vgamma clones among the…