High-grade Malignant Lymphoma Research Articles

Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma.

Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.

Extranasal T/NK lymphoma with a fatal outcome: A case report

Extranodal T/NK lymphoma (LTNKEN) is a rare and aggressive form of non-Hodgkin lymphoma of high-grade malignancy. A distinction is made between the nasal forms, characterized by primary involvement of the nasal cavity, and the extranasal forms. Primary skin involvement is highly rare. Diagnosis is based on immunohistochemical studies. Treatment includes chemotherapy and radiotherapy. This type of lymphoma has a poor prognosis even with treatment. Herein, we report a Moroccan case of cutaneous T/NK lymphoma in a young patient with a primary cutaneous localization of fatal evolution. Key words: Lymphoma; Extranodal lymphoma; T/NK lymphoma; Non-hodgkin lymphoma

BREAST LYMPHOMA

Primary breast lymphoma is a very rare histological entity of breast cancer. The Clinical and radiological aspects do not present any particular specificities. Diagnosis is often delayed. The treatment is mainly based on chemotherapy. We report the case of a patient with high grade malignant non-Hodgkin lymphoma. The symptomatology was made of breast swelling. The remote extension assessment was negative. The patient received 6 courses of type R mini CHOP chemotherapy followed by three-dimensional radiotherapy with a dose of 30 Gy in 15 fractions for 3 weeks. An echo mammography in between treatment showed: a partial response at 50%. Controle PET CT scan performed 3 weeks after the last cure having objectified: Complete disappearance of the active subcutaneous nodule at the level of the QSE of the right breast. Breast localisation of lymphoma is very rare. His prognosis was considerably improved due to a multidisciplinary approach.

Overview of Gastrointestinal Lymphoproliferative disorders✰.

Lymphoproliferative processes which occur in the gastrointestinal tract range from benign reactive processes such as follicular hyperplasia (rectal tonsil) to high grade malignant lymphomas and histiocytic sarcoma. The WHO Classification of Tumors: Digestive System Tumors, 5th Edition was published in 2019 and shows several impactful changes as compared to the 4th Edition published in 2010. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues 2017 also included detailed changes in hematopoietic neoplasms within the gastrointestinal tract. New entities or renamed hematolymphoid lesions include monomorphic epitheliotropic intestinal T-cell lymphoma, duodenal-type follicular lymphoma, intestinal T-cell lymphoma, NOS and indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. A brief overview of WHO classification of digestive tumors and WHO classification of tumors of hematopoietic and lymphoid tissue is discussed focusing on the changes in the most recent WHO texts. In depth discussions will be presented in other papers in this series.

Subclassification of Diffuse Large B-Cell Lymphomas According to the Kiel Classification: Distinction of Centroblastic and Immunoblastic Lymphomas Is a Significant Prognostic Risk Factor

AbstractAmong high-grade malignant non-Hodgkin's lymphomas the updated Kiel classification identifies three major B-cell entities: centroblastic (CB), B-immunoblastic (B-IB), and B-large cell anaplastic (Ki-1+) (now termed anaplastic large cell [CD30+], [B-ALC]). The clinical prognostic relevance of this distinction was evaluated in a randomized prospective treatment trial (COP-BLAM/IMVP-16 regimen randomly combined ± radiotherapy in complete responders) conducted in adult (age 15 to 75) patients with Ann Arbor stage II-IV disease (n = 219) diagnosed by optimal histomorphology (Giemsa staining) and by immunohistochemistry. Overall survival was significantly better in CB lymphoma as compared to B-IB (P = .0002) or B-ALC (P = .046). Relapse-free survival was worse for B-IB (P = .0003) as compared to CB lymphomas. The prognostic differences between CB and B-IB were confirmed by multivariate analyses including the risk factors of the International Index. Overall survival was significantly determined by performance status (P = .0003), serum-LDH (P = .036), and B-IB histology subtype (P = .036). Relapse-free survival was influenced by age (P = .007) and histological subtype (P = .007). Thus, the diagnosis of the CB and B-IB lymphomas by the histological criteria of the Kiel classification was identified as an independent prognostic factor in diffuse large B-cell lymphomas.

Clinical And Prognostic Features Of Non Hodgkin Lymphoma And Preliminary Effective Evaluation Of R-Chop Regimen In Patients With Diffuse Large B-Cell Lymphoma

Background: WHO 2008 classification of Non Hodgkin Lymphoma (NHL) has been introduced and got consensus internationally. However, studies on NHL according to WHO 2008 classification are limited in Vietnam. In terms of treatment, the R-CHOP regimen is still the most commonly used regimen for the treatment of moderate or high grade malignant lymphoma tumors. However, its effectiveness on each type has not been specifically studied. Purpose of this research is to evaluate of clinical and subclinical characteristics of NHL patients according to the 2008 WHO classification on lymphoid neoplasms and to evaluate preliminary effective of diffuse large B cell lymphoma (DLBCL) patients with R-CHOP regimen. Materials and methods: A prospective descriptive study was conducted on 48 patients diagnosed with NHL undergoing treatment at the Hue University Hospital from July 2019 and Hue Central Hospital from April 2020 to present. Results: The mean age was 52.4 years, male/female ratio = 1.3/1, the most common primary tumor site was lymph nodes with 54.3%. Stage IV was found in 37.5% of all cases. DLBCL was the most common type, accounted for 58.3%, whereas marginal zone lymphoma had the lowest incidence (2.1%). According to the International Prognostic Index (IPI), low risk, low-intermediate risk, high-intermediate risk, high risk group were 43.6%; 25.0%; 18.8%; 12.6% respectively. 34.8% patients responsed completely after 3 cycles and after 6 – 8 cycles, 58.8% patients achieved complete response. Grade III, IV neutropenia, grade I, II peripheral neuropathy and grade I, II thrompocytopenia were the most common side effect observed. Conclusions: DLBCL is the most common Non Hodgkin Lymphoma. R-CHOP regimen has a good response after 6-8 cycles in DLBCL diseases and is well tolerated that the adverse events are mostly able to control effectively.

Epstein-Barr virus–specific cytokine-induced killer cells for treatment of Epstein-Barr virus–related malignant lymphoma

BackgroundProlonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context. MethodsCIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool. CIK cells with EBV-specificity and conventional CIK cells were phenotypically and functionally analyzed. Additionally, CIK cells with EBV-specificity were applied to a patient with EBV-related PTLD rapidly progressing to highly aggressive B-cell lymphoma on a compassionate use basis after approval and agreement by the regulatory authorities. ResultsPre-clinical analysis showed that generation of CIK cells with EBV-specificity was feasible. In vitro cytotoxicity analyses showed increased lysis of EBV-positive target cells, enhanced proliferative capacity and increased secretion of cytolytic and proinflammatory cytokines in the presence of EBV peptide-displaying target cells. In addition, 1 week after infusion of CIK cells with EBV-specificity, the patient's highly aggressive B-cell lymphoma persistently disappeared. CIK cells with EBV-specificity remained detectable for up to 32 days after infusion and infusion did not result in acute toxicity. DiscussionThe transfer of both anti-cancer potential and T-cell memory against EBV infection provided by EBV peptide-induced CIK cells might be considered a therapy for EBV-related PTLD.

An Unusual Posttransplant T-cell Lymphoma After Liver Transplantation: A Case Report

Posttransplantation lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities ranging from benign lymphocytic proliferations to high-grade malignant lymphomas. The majority of PTLDs are associated with reactivation of Epstein-Barr virus (EBV), which induces B-cell proliferation and occurs in the setting of severe immune suppression after solid organ or bone marrow transplantation. T-cell/natural killer cell PTLDs are relatively rare, constituting ∼15% of all cases. T-cell PTLDs are usually aggressive, and outcomes are poor. This article describes an unusual case of T-cell PTLD with a favorable outcome. The patient is a 57-year-old man who underwent a liver transplantation due to hepatitis C cirrhosis. He developed graft-versus-host disease with skin and gastrointestinal involvement and generalized lymphadenopathy 4 months after transplantation. Histologic sections of an excised axillary lymph node showed atypical medium and larger T-lymphocytes that were positive for CD3, CD5, CD43, and CD8 but were negative for B-cell antigens, CD56, and in situ hybridization for EBV-encoded RNA. Polymerase chain reaction analysis revealed monoclonal T-cell receptor gamma chain gene rearrangement. A diagnosis of high-grade T-cell PTLD was made. The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone and is currently in remission, 4 years after therapy. The rapid presentation of an EBV-negative T-cell PTLD with a nonaggressive course and complete response to treatment is an unusual presentation of posttransplantation T-cell lymphoma, which is usually associated with a high mortality rate.

Intraoperative Mapping and Monitoring of the Pyramidal Tract Using Endoscopic Depth Electrodes.

To evaluate motor function during neuroendoscopic resectioning of deep-seated brain tumors using endoscopically guided depth electrodes. For 12 cases of thalamic tumors, including high-grade gliomas, germinomas, and malignant lymphomas, depth electrodes were inserted using endoscopic guides between the tumor and the pyramidal tract in the thalamus. Motor-evoked potentials (MEPs) were continuously recorded during neuroendoscopic resectioning of the tumors. Monitoring of MEP responses using depth electrodes in all 12 cases was successful. The minimum stimulus intensity threshold required to induce MEP responses was 3 mA. Gross total or subtotal resections were successful with this technique for all patients with glioma. No additional neurologic impairments were found after surgery in any of the cases. Continuous MEP measurement using depth electrodes can serve as a new monitoring technique for endoscopic resectioning of deep-seated brain tumors.

Bilateral Adrenal Primary Diffuse Large B-Cell Lymphoma not Accompanied by Adrenal Insufficiency: A Report of Two Cases

Primary adrenal lymphoma (PAL) is uncommon in clinical settings, which is considered a rare high grade malignant lymphoma with a poor prognosis, patients with bilateral mass are rarer, and patients with normal adrenal function are extremely rare. We present 2 cases of patients with bilateral adrenal primary diffuse large B-cell lymphoma (PA-DLBCL) whose adrenal functions were normal. 2 patients were treated with unilateral adrenalectomy and a combination of chemotherapy. We summarized cases, reviewed the literature and discussed important issues with regard to the pathology change, diagnosis, treatment and prognosis.

Lymphocryptovirus-dependent occurrence of lymphoma in SIV-infected rhesus macaques with particular consideration to two uncommon cases of non-Hodgkin's lymphoma

Abstract. Despite combination antiretroviral therapy, high-grade malignant non-Hodgkin's lymphoma (NHL) is still one of the most frequently acquired immunodeficiency syndrome (AIDS)-defining disorders in the end stage of infection with human immunodeficiency virus (HIV). NHL can also be observed in rhesus macaques infected with the simian immunodeficiency virus (SIV). Thus, they represent a useful model to study morphological characteristics and oncogenetic mechanisms of NHL in humans.When reviewing the occurrence of lymphoma at the German Primate Center over the past 25 years within the context of pathogenic SIV infection we noticed a strikingly high incidence (four out of seven animals) of these tumors in rhesus macaques infected with ex vivo derived SIVmac251/32H/spleen in AIDS-defining end-stage disease. Polymerase chain reaction analysis of this virus stock revealed the co-presence of rhesus lymphocryptovirus (rhLCV), which represents the monkey homologue to human Epstein–Barr virus (EBV), suggesting an association between co-application of SIV and rhLCV and increased tumorigenesis.In addition, we present two cases of NHL in rhesus macaques infected with a SIVmac239 nef-mutant variant because one exhibited an unusual immunophenotype and the other an uncommon organ manifestation. Histological and immunohistochemical examinations of tumors of the first animal revealed metastatic diffuse large B-cell lymphomas (DLBCL) affecting the stomach and the pancreaticoduodenal lymph nodes, of which the one in the stomach presented the rare dual expression of CD20 and CD3. Necropsy of the second animal revealed an obstructive DLBCL around the urinary bladder neck that led to urine backflow and eventually death due to acute uremia without any further AIDS-like manifestations. In the tumors of both animals, abundant Epstein–Barr nuclear antigen-2 expression was demonstrated, thus verifying concurrent rhLCV infection. Flow cytometric analyses revealed a high percentage of activation as well as proliferation in B cells from peripheral lymph nodes in both animals. Moreover, CD4+ T cells were depleted in blood, colon and lymphoid tissue. Concomitantly, CD8+ T cells showed an exhausted phenotype. The two case reports and the increased incidence of NHL following co-application of SIV and rhLCV underline the role of rhLCV in lymphomagenesis.

Epstein-Barr virus (EBV)-associated lymphoid lesions of the head and neck.

Epstein Barr virus (EBV)-related lymphoproliferative processes occur in the head and neck ranging from reactive processes such as infectious mononucleosis to high grade malignant lymphomas. EBV is a ubiquitous herpes virus that infects more than 90% of adults worldwide, and is generally transferred though saliva. Primary infection can occur throughout life. EBV is the first virus linked to malignancies, both epithelial and lymphoid. Both T and B cell lymphomas can be associated with EBV and evidence shows that an individual's response to the acute EBV infection may be critical in the development of subsequent lymphoma. Currently, in situ hybridization for EBER is the most sensitive available test to detect EBV and should be routinely performed in lymphoproliferative lesions of the head and neck. Immunohistochemistry for EBV related proteins, such as LMP1, is much less sensitive than EBER in situ hybridization, but can help determine latency patterns of EBV infection. Although relatively rare, primary EBV-related lymphomas must be considered in the differential of atypical lymphoid proliferations in the head and neck. We present selected EBV-related disorders of the head and neck discussing etiology as well as differential diagnosis.

An Unusual Cause of Melena

FIGURE 2. A, Computed tomography of the abdomen exhibited a pancreas body-tail mass with direct invasion of the gastric wall. B, Wholebody dual-modality 18F-fluorodeoxyglucose positron emission tomography/ computed tomography images disclosed multiple areas with increased 18F-fluorodeoxyglucose uptake around the stomach, pancreas, and several nodes over the substernal and superior mediastinum region. From the Division of Internal Medicine, Department of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. A 47-year-old man was hospitalized after experiencing melena and vomiting for 1 day. He also had intermittent epigastric pain concurrent with weight loss from 89 kg to 75 kg over 1 month. His own and his family’s medical histories were unremarkable. Physical examination showed epigastric tenderness without rebound pain. Initial laboratory examination revealed abnormalities as follows: leukocyte counts, 11.86 10/mL; hemoglobin level, 12.5 g/dL; blood urea nitrogen, 47 mg/dL; and creatinine, 1.4 mg/dL. Upper gastrointestinal endoscopy identified an ulcerative mass over the lower body of the stomach. Biopsies demonstrated highgrade malignant B-cell lymphoma of the gastric tissue (Figure 1, A). Immunohistochemically, the tumor cells were positive for CD20 (Figure 1, B) and Bcl-2, but negative for CK and CD3. Computed tomography of the abdomen exhibited a pancreas body-tail mass with direct invasion of the gastric wall (Figure 2, A). Whole-body dual-modality 18F-fluorodeoxyglucose positron emission tomography/computed tomography images disclosed multiple areas with increased 18Ffluorodeoxyglucose uptake around the stomach, pancreas, and several nodes over the substernal and superior mediastinum region (Figure 2, B). Primary pancreas lymphoma was excluded because of mediastinum nodal involvement and leukocytosis based on Behrns’ diagnostic criteria. Secondary malignant B-cell lymphoma of the pancreas was confirmed. Although non-Hodgkin lymphoma with secondary involvement of the pancreas is estimated to occur in about 30% to 40% of non-Hodgkin lymphoma cases, melena due to secondary malignant B-cell lymphoma of the pancreas with direct invasion of the stomach has not been reported in the literature. Our patient received the standard chemotherapy protocol for non-Hodgkin lymphoma.

C-Myc and E2F1 drive PBK/TOPK expression in high-grade malignant lymphomas

c-Myc has been implicated in a variety of hematologic malignancies including Burkitt's lymphoma. Targeting c-Myc driven growth pathways could be therapeutically useful but might require the identification of critical downstream proteins. Here we show that the serine–threonine kinase PBK/TOPK is frequently overexpressed in high-grade lymphomas and its expression is positively correlated to that of c-Myc and E2F1. Further we demonstrate that c-Myc regulates PBK expression through E2F1. Additionally, inhibition of c-Myc, E2F1 or PBK comparably decreased cell growth and survival. In conclusion, a c-Myc–E2F1–PBK signaling pathway operates in high-grade lymphomas and may provide a useful target for novel antineoplastic therapeutics.

V.-cava-inferior-Thrombose bei Patientin mit Non-Hodgkin-Lymphom und stattgefundener Wirbelsäulenoperation

Complete or partial thrombosis of the inferior vena cava is usually due to pre-existing malformation of the vessel, malignant tumors, ascending thrombosis, or thrombophilic disorders. We report the case of an 81-year-old woman, in whom a partial thrombosis of the vena cava was observed in the CT scan when re-staging was performed after six cycles of R-CHOP because of high-grade malignant non-Hodgkin lymphoma. Before chemotherapy was started, the patient had undergone an operation of the lumbar spine using cement augmentation. Retrospective analysis showed that cement had penetrated a segmental vein and spilled into the vena cava leading to formation of an adhering blood thrombus. The patient was free of symptoms and anticoagulation was started. Spillage of cement frequently occurs in the process of vertebroplasty and kyphoplasty and may result in serious sequelae. As these procedures are increasingly being used, physicians should be aware of these complications if a patient presents with thrombosis of the caval vein or signs of pulmonary embolism.

Lymphoproliferative Disorder and Acquired C1-INH Deficiency. A Case Series of 48 Patients

Abstract 1596Angioedema with acquired deficiency of C1 inhibitor (C1-INH) is a rare syndrome associated with B lymphocyte disorders, usually identified as acquired angioedema (AAE). The clinical features of C1-INH deficiency, more often of genetic origin (hereditary angioedema HAE), include subcutaneous swelling, edema of the gastrointestinal wall causing temporary bowel obstruction with severe pain and edema of the upper respiratory tract that can lead to asphyxia. AAE associated B cell disorders result in autoantibodies to C1-INH, monoclonal gammopathies of uncertain significance (MGUS) and non Hodgkin Lymphomas (NHL). The 3 conditions may be concomitantly present suggesting that expansion of an anti C1-INH B lymphocyte clone is the primum movens of the disease. The burden of AAE derives from either the associated limphoproliferative disorder or the frequency and severity of angioedema symptoms: both conditions may lead to death. Here we report on the long term follow up of 48 patients (median age at onset of angioedema symptoms 57, range 39/79) with AAE with specific focus on the fate of lymphoproliferative disease and on the therapeutic problems. Patients were followed for a median of 6 years ( 1–25); diagnosis was based on C1-INH activity <50% of normal. Autoantibodies to C1-INH were positive in 35 of 48 patients (13 IgG, 13 IgM, 5 IgA, 2 IgG-IgM, 2 IgA-IgM). Nineteen (40%) fulfilled diagnostic criteria for MGUS. MGUS and auto antibodies to C1-INH coexisted in 13 patients all, but one, sharing the same heavy chain isotype. In 7, binding of the M component to purified C1-INH could be demonstrated. Twelve patients presented NHL. Based on WHO classification 10 had indolent lymphoma (2 lymphoplasmocytic/Waldestrom disease; 4 small lymphocytic lymphoma, 4 splenic marginal zone lymphoma, 1 follicular lymphoma). Median time between onset of angioedema symptom and diagnosis of NHL was 1 year (ranging from 15 years before to 12 years after). One lymphocytic and 1 marginal splenic lymphoma did not need treatment at 5 and 8 years follow up respectively. Two marginal splenic lymphoma are in remission after splenectomy at 2 and 7 years follow up. One marginal splenic lymphoma remitted upon splenectomy, chemotherapy and rituximab (3 years follow up). One lymphoplasmocytic lymphoma is in remission 2 years after rituximab. Two lymphocytic lymphoma remain on control with chemotherapy at 16 and 3 years respectively. One lymphoplasmocytic lymphoma progessed to death despite chemotherapy and rituximab. One follicular lymphoma is in remission 6 years after chemotherapy. Two high grade malignant lymphoma, a large B cell and a mantle cell, both progressed to death within 12 months despite chemotherapy and splenectomy the first and chemotherapy the second. Reversal of complement abnormalities was achieved upon therapy induced remission of NHL. Because of the frequency of angioedema recurrences 28 patients required prophylactic treatment successfully achieved with tranexamic acid in 23 patients and with danazol in 5. Breakthrough angioedema attacks were treated with plasma derived C1-INH, which was effective in 16 patients and non effective in 8. In these 8 patients, angioedema attacks were successfully treated with icatibant, a specific antagonist of the B2 receptors of bradykinin, the mediator of symptoms (median time to resolution 6.75 hours, range 0.5–39.75 hours). Ecallantide, a recombinant small protein that blocks plasma kallikrein, the bradykinin releasing enzyme, has also been successfully used to treat two angioedema attacks in two patients. During the follow up period 5 patients died for causes other than NHL or angioedema and one patient is in irreversible cerebral coma for severe hypoxia following a laryngeal edema, which did not respond to plasma derived C1-INH (icatibant was not available at that time). Our data suggest that in AAE different forms of B cells disorders coexist and/or evolve into each other probably starting from the pathologic prolypheration of clone(s) autoreactive against C1-INH. Hence, angioedema symptoms and B cell disorders are two aspect of a single disease. Blocking bradykinin or its release are valid alternatives to treat angioedema symptoms and may be lifesaving therapies for those patients who do not respond to plasma derived C1-INH. Disclosures:Off Label Use: Icatibant, a specific antagonist of the B2 receptors of bradykinin, registered in Europe for the treatment of acute attacks in patients with Hereditary Angioedema. Zanichelli:Shire: Membership on an entity's Board of Directors or advisory committees. Cicardi:Shire: Consultancy, Speakers Bureau; Dyax: Consultancy, Speakers Bureau.

Navigation-Guided Endoscopic Biopsy for Intraparenchymal Brain Tumor

To evaluate the efficacy of intraparenchymal brain tumor biopsy using endoscopy and a navigation system (navigation-guided endoscopic biopsy) as a diagnostic tool, a case series of intraparenchymal tumor biopsies was reviewed. Navigation-guided endoscopic biopsy was applied in 9 cases, stereotactic needle biopsy in 16 cases, and open biopsy with or without navigation system in 34 cases. In all biopsy cases, 84.7% of biopsy points were sampled accurately, and 93.2% of diagnoses by biopsy were correct. Comparison of each type of biopsy showed that the resected volumes in navigation-guided endoscopic biopsy and open biopsy tended to be larger than those in stereotactic biopsy, and the mean operation time for the open biopsy procedure was the longest. To define the most applicable device or examination method to increase sampling accuracy, various factors were analyzed in 59 procedures. Navigation-guided endoscopic biopsy was the most accurate of the three types of biopsy, although the statistical difference was not significant. Older patients, histological diagnosis of high-grade glioma or malignant lymphoma, positive photodynamic diagnosis, and positive intraoperative pathology were significant factors in improving the sampling accuracy. Navigation-guided endoscopic biopsy could provide a larger sample volume within a relatively short operation time. The biopsy can be easily combined with both photodynamic diagnosis and intraoperative pathology, significantly improving the histological diagnostic yield.

Progression of Nodular Lymphocyte-Predominant Hodgkin?s Lymphoma to a High-Grade Lymphoma

Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) is a rare subtype of Hodgkin’s lymphoma characterized by a nodular proliferation of large neoplastic B cells that are CD15 and CD30 negative. Although this neoplasm develops slowly and has a favorable prognosis with Stage I or II disease, it has a high rate of recurrence and patients tend to have repeated relapses [1]. Increasingly, reports have shown that a small percentage of patients with NLPHL may transform to a more aggressive lymphoma concurrently or many years later. This case highlights a 58 year-old man who developed NLPHL at age 33 and progressed to a high-grade malignant lymphoma 25 years later. The purpose of this report is to share this patient’s unusual clinical course and provide a pertinent literature review of NLPHL.

Sirolimus addition to tacrolimus-based immunosuppression induces complete remission of post-transplant lymphoproliferative disorder in a liver transplant recipient

Sirolimus addition to tacrolimus-based immunosuppression induces complete remission of post-transplant lymphoproliferative disorder in a liver transplant recipient

Differential expression of Toll-like receptors in follicular lymphoma, diffuse large B-cell lymphoma and peripheral T-cell lymphoma

Although Toll-like receptors (TLRs) in mammals are well-known to play important roles in innate immunity, newer roles for the TLRs have suggested that cells with aberrant TLR expression may have a survival advantage over normal cells. Lymphocytes are one of a small number of cell types that express many of the TLRs, suggesting that abnormal TLR levels/signaling may potentially influence the progression of malignant lymphomas. Thus, frozen samples of 51 lymph nodes from patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) were analyzed for the expression of TLR1 to 9 using quantitative real-time PCR, and compared to those in reactive lymphadenopathy (RL) samples. TLR2 was over-expressed in both DLBCL and PTCL but not in FL when compared to RL. TLR1 and TLR4 expression was up-regulated in PTCL, while TLR8 was highly expressed in DLBCL. Although TLR5 showed lower expression in FL, expression of TLR3, TLR6, TLR7 and TLR9 did not vary significantly between different lymphoma subtypes. Double immunostaining revealed an increase in the number of TLR2 and/or TLR8 expressing lymphoma cells in DLBCL. In PTCL, TLR2 and TLR4 expression was localized to neoplastic T cells. TLR expression is highly variable among lymphoma subtypes. However, despite this some significant differences exist that may prove useful in the development of novel therapeutic strategies.