CLINICAL AND LABORATORY FEATURES OF ANTICENTROMERE ANTIBODY-POSITIVE SJö GREN’S SYNDROME

2019 ◽  
Vol 57 (4) ◽  
pp. 431-439
Author(s):  
B. D. Chaltsev ◽  
V. I. Vasilyev ◽  
S. G. Palshina ◽  
A. V. Torgashina ◽  
E. V. Sokol ◽  
...  
Keyword(s):  
B Cell ◽  
Patient Group ◽  
Malt Lymphoma ◽  
World Health ◽  
Biliary Cirrhosis ◽  
Anticentromere Antibody ◽  
Detection Rates ◽  
Biopsy Specimens ◽  
Laboratory Features ◽  
Immunohistochemical Studies

Objective: to study the clinical and laboratory features of patients with anticentromere antibody (ACA) positive Sjö gren’s syndrome (SjS); to assess the spectrum of autoantibodies in patients of this group; to determine the frequency with which the SjS patients who are highly positive for ACA, meet the international classification criteria for SjS and systemic sclerosis (SS); to reveal the incidence of MALT lymphomas in this patient group; to estimate the incidence of primary biliary cirrhosis (PBC)/biliary lesions as part of autoimmune epithelitis in SjS in this patient group.Material and methods. A total of 83 patients with ACA positive SjS were comprehensively examined at the V.A. Nasonova Research Institute of Rheumatology during the period 2012 to 2018. The inclusion criteria were con formity to the 2001 Russian SjS criteria and a high ACA level. MALT lymphomas were diagnosed on the basis of histological and immunohistochemical studies and polymerase chain reaction-based determination of B-cell clonality in the biopsy samples of affected organs according to the World Health Organization classification of Hematopoietic Tumors. The diagnosis of PBC/biliary lesions was made on the basis of histological and immunohistochemical studies of liver biopsy specimens.Results and discussion. The investigation revealed low detection rates for anti-Ro antibodies (32.5%), anti-La antibodies (7.2%) and rheumatoid factor (RF) (21.7%), which were typical for the classical SjS immunophenotype), increased ESR (14%), leukopenia (7%), hypergammaglobulinemia (17.6%), elevated levels of IgG (9.5%) and IgA (18.7%), and hypocomplementemia (16.1%) in the ACA positive SjS patients. Despite the low detection rate of RF, 15 (18%) patients in this group developed MALT lymphomas: 14 patients had salivary gland MALT lymphoma and one patient had tonsil MALT lymphoma with peripheral lymph node involvement (generalized marginal zone lymphoma). Also, the patients of this group showed high detection rates for AMA antibodies (34.6%), increased IgM level (29.7%) and a higher risk for PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS (14.5%). AMA-antibodies were absent in only two patients who were diagnosed with liver disease according to biopsy specimens. Nervous system and renal lesions, antiphospholipid syndrome, rheumatoid arthritis, hypergammaglobulinemic purpura, and cryoglobulinemic vasculitis were much less common and sporadic. Also ACA-positive SjS patients often have Raynaud’s phenomenon (54.9%) with scleroderma-type capillaroscopic changes (68%) and a limited form of SS (24%) according to the 2013 ACR criteria.Conclusion. ACA-positive SjS is a subtype of the disease, which is significantly different from the classic one in a number of clinical and laboratory signs and characterized by an increased risk for SS, MALT lymphomas, and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS which in some cases leads to the underdiagnosis of SjS. ACA should be considered as pathogenetically related to SjS autoantibodies; and all patients who are seropositive for ACA should be examined for SjS and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS regardless of whether they have SS or not, as well as complaints of dry mouth and eyes. Patients with significantly enlarged salivary glands should undergo biopsy to rule out or confirm MALT lymphoma before initiating hormonal, antilymphoproliferative, and anti-B-cell therapy.

T(X;14)(p11.4;q32.33) Is Recurrent In Marginal Zone Lymphoma and Upregulates GPR34

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1349-1349
Author(s):  
Iwona Wlodarska ◽  
Julio Finalet Ferreiro ◽  
Thomas Tousseyn ◽  
Helena Urbankova ◽  
Lucienne Michaux ◽  
...  
Keyword(s):  
B Cell ◽  
Malt Lymphoma ◽  
Target Genes ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
World Health ◽  
Signal Pathways ◽  
Transcript Levels

Abstract Abstract 1349 Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) and nodal MZL are recognized as distinct entities in the World Health Organization classification of lymphoid tumors. So far, genetic events underlying pathogenesis of both malignancies are incompletely understood. It has been shown, however, that approximately 25% of MALT lymphoma cases are hallmarked by recurrent chromosomal translocations including t(11;18)(q21:q21) leading to an API2 -MALT1 fusion and IGH-mediated t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p14;q32) targeting the BCL10, MALT1 and FOXP1 genes, respectively. Notably, the BCL10 and MALT1 proteins play a physiological role in antigen receptor mediated activation of the nuclear factor-κB (NF-κB) signaling pathway, known to be implicated in tumor growth, survival and chemoresistance. We report here a novel IGH-associated translocation t(X;14)(p11.4;q32.33), that was identified in 2 cases of MALT lymphoma and single cases of nodal MZL and gastric diffuse large B-cell lymphoma (DLBCL). Of note, all 4 patients had an underlying disorder, including Sjögren's syndrome (2 patients with MALT lymphoma), a leukocytoclastic vasculitis and polyneuropathy (MZL) and HP-negative chronic gastritis with intestinal metaplasia (DLBCL). There were 3 female patients and 1 male patient in age ranging from 66 to 82 years (median 75 years). All patients received an initial therapy. Two patients are alive after 42–54 months from diagnosis and 2 died, either from progressive lymphoma, or from unrelated cause (other tumor). In each patient, t(X;14) was identified at the time of lymphoma diagnosis. The translocation occurred as the sole abnormality in 1 case and was accompanied by 2 to 4 additional chromosomal abnormalities in other cases. Mapping of the Xp11.4 breakpoint was performed by fluorescence in situ hybridization (FISH) using tilepath BAC clones. The breakpoint was eventually located in the region of CASK that hosts GPR34 and GPR82, two genes encoding G-protein coupled receptors. Expression of 5 candidate target genes was tested by qRT-PCR. This analysis showed that only 1 of the analyzed genes, GPR34, was upregulated 11–100 fold in 3 studied cases. An aberrant expression of GPR34 protein in these tumors has been demonstrated by immunohistochemistry. GPR34 belongs to the largest family of cell surface molecules involved in signal transmission that play important roles in many physiological and pathological processes, including tumorigenesis. As constitutive NF-κB activity is frequently associated with B-cell lymphoma development, we examined whether the NF-κB pathway was active in 3 lymphomas with t(X;14) from which material was available. In all of them Western blot analysis showed phosphorylation of the NF-κB inhibitor protein Iκ-Bα, which indicates its degradation and is a hallmark of activation of NF-κB pathway. Jurkat T cells stimulated with PMA/Ionomycin served as a positive control. Quantitative RT-PCR further confirmed upregulation of a number of NF-κB target genes in t(X;14) lymphoma samples, with transcript levels comparable to a t(11;18)-positive MALT lymphoma. To examine the role for GPR34 in NF-κB activation, we overexpressed GPR34 in the B-cell lymphoma cell line BJAB, in which the NF-κB pathway is relatively quiescent. Although GPR34 transcript levels increased 40 to 800 fold, the set of NF-κB target genes was not upregulated, in contrast to its induced upregulation by overexpression of API2-MALT1 or mutant CARD11 (L232LI), known activators of NF-κB signaling in B-cells. These data suggest that activation of NF-κB signaling in MALT lymphomas with t(X;14) is not mediated by GPR34 overexpression and most likely involves other mechanisms. In conclusion, we identified GPR34 as a new player of B-NHL pathogenesis. The gene is recurrently targeted by the IGH-mediated t(X;14)(p11.4;q32.33) associated with MZ/MALT lymphoma evolving from a previous auto-immune disorder. The functional consequences of t(X;14) remain elusive, but our data indicate that upregulated GPR34 does not activate NF-κB. Although studies are required to determine GPR34 natural ligand(s) and signal pathways, this protein is definitely a very promising novel target for treatment of lymphoma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Low-cost transcriptional diagnostic to accurately categorize lymphomas in low- and middle-income countries

2021 ◽  
Vol 5 (10) ◽  
pp. 2447-2455
Author(s):  
Fabiola Valvert ◽  
Oscar Silva ◽  
Elizabeth Solórzano-Ortiz ◽  
Maneka Puligandla ◽  
Marcos Mauricio Siliézar Tala ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
B Cell ◽  
The United States ◽  
World Health ◽  
Middle Income ◽  
Chemical Ligation ◽  
Middle Income Countries ◽  
Biopsy Specimens ◽  
Extreme Gradient Boosting

Abstract Inadequate diagnostics compromise cancer care across lower- and middle-income countries (LMICs). We hypothesized that an inexpensive gene expression assay using paraffin-embedded biopsy specimens from LMICs could distinguish lymphoma subtypes without pathologist input. We reviewed all biopsy specimens obtained at the Instituto de Cancerología y Hospital Dr. Bernardo Del Valle in Guatemala City between 2006 and 2018 for suspicion of lymphoma. Diagnoses were established based on the World Health Organization classification and then binned into 9 categories: nonmalignant, aggressive B-cell, diffuse large B-cell, follicular, Hodgkin, mantle cell, marginal zone, natural killer/T-cell, or mature T-cell lymphoma. We established a chemical ligation probe-based assay (CLPA) that quantifies expression of 37 genes by capillary electrophoresis with reagent/consumable cost of approximately $10/sample. To assign bins based on gene expression, 13 models were evaluated as candidate base learners, and class probabilities from each model were then used as predictors in an extreme gradient boosting super learner. Cases with call probabilities < 60% were classified as indeterminate. Four (2%) of 194 biopsy specimens in storage <3 years experienced assay failure. Diagnostic samples were divided into 70% (n = 397) training and 30% (n = 163) validation cohorts. Overall accuracy for the validation cohort was 86% (95% confidence interval [CI]: 80%-91%). After excluding 28 (17%) indeterminate calls, accuracy increased to 94% (95% CI: 89%-97%). Concordance was 97% for a set of high-probability calls (n = 37) assayed by CLPA in both the United States and Guatemala. Accuracy for a cohort of relapsed/refractory biopsy specimens (n = 39) was 79% and 88%, respectively, after excluding indeterminate cases. Machine-learning analysis of gene expression accurately classifies paraffin-embedded lymphoma biopsy specimens and could transform diagnosis in LMICs.

Primary Hepatic Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type in a Patient With Primary Biliary Cirrhosis

2000 ◽  
Vol 124 (4) ◽  
pp. 604-608 ◽  
Author(s):  
Ming Q. Ye ◽  
Arief Suriawinata ◽  
Candice Black ◽  
Albert D. Min ◽  
James Strauchen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Primary Biliary Cirrhosis ◽  
B Cell ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tissue Type ◽  
Biliary Cirrhosis

Abstract Primary lymphoma of the liver is rare. Recently, marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type have been described in the liver. Most of these cases occurred without known underlying liver disease, while others were seen in patients with chronic hepatitis. A case of primary hepatic MALT lymphoma in a patient with primary biliary cirrhosis was reported recently. Some authors have proposed that chronic persistent immunogenic stimulation causes development of acquired MALT and subsequently MALT lymphoma, based on the observation of MALT lymphoma in association with infectious agents, such as Helicobacter pylori and hepatitis C virus, and autoimmune diseases, such as Hashimoto thyroiditis and Sjögren syndrome. Primary biliary cirrhosis is a chronic, progressive, cholestatic liver disease characterized by destruction of intrahepatic small to medium-sized bile ducts; this disease is mediated by a cytotoxic T-cell reaction. The prolonged immune activation in primary biliary cirrhosis may play a role in the lymphomagenesis of hepatic MALT lymphoma. We describe another case of primary hepatic MALT lymphoma, which was found incidentally in a patient with end-stage primary biliary cirrhosis. This case further supports the role of immunogenic stimulation in the pathogenesis of this particular low-grade B-cell lymphoma.

Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL

2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
High Grade ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Health Organization ◽  
Large B Cell

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.

scholarly journals Quality of life in patients with narcolepsy: a WHOQOL-bref study

2008 ◽  
Vol 66 (2a) ◽  
pp. 163-167 ◽  
Author(s):  
Heloísa Rovere ◽  
Sueli Rossini ◽  
Rubens Reimão
Keyword(s):  
Quality Of Life ◽  
Patient Group ◽  
World Health ◽  
Control Group ◽  
World Health Organization Quality ◽  
Severe Impairment ◽  
Perception Of Quality ◽  
Social Domains ◽  
Health Organization

OBJECTIVE: To evaluate the perception of Quality of Life (QL) in Brazilian patients with narcolepsy. METHOD: 40 adult patients aged between 20 and 72 years (mean=41.55; SD=14.50); (28 F; 12M), with the diagnosis of chronic narcolepsy were followed up at the outpatient clinic (Patient Group). The Control Group was composed of 40 adults. The instrument utilized was the World Health Organization Quality of Life (WHOQOL-BREF). RESULTS: The two groups were homogeneous and no difference was found with regards to age, sex, and demographic characteristics. The perception of QL in physical, psychological and social domains showed lower scores in those patients with narcolepsy than in the control group (p<0.05). Concerning physical domain, all the aspects evaluated were significantly impaired, in patient group, including sleep satisfaction (p<0.001); energy for daily activities (p=0.039); capacity to perform activities (p=0.001); and capacity to work (p=0.001). CONCLUSION: The perception of QL showed severe impairment in patients with narcolepsy for physical, psychological and social domains.

scholarly journals How I treat double-hit lymphoma

Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 590-596 ◽  
Author(s):  
Jonathan W. Friedberg
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Involvement ◽  
B Cell Lymphoma ◽  
World Health ◽  
Large B Cell Lymphoma ◽  
Double Hit Lymphoma ◽  
Increased Risk ◽  
Double Hit ◽  
Large B Cell

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

Synchronous Interdigitating Dendritic Cell Sarcoma and B-Cell Small Lymphocytic Lymphoma in a Lymph Node

2006 ◽  
Vol 130 (4) ◽  
pp. 544-547
Author(s):  
Antonio Cossu ◽  
Angelo Deiana ◽  
Amelia Lissia ◽  
Maria Filomena Dedola ◽  
Lucia Cocco ◽  
...  
Keyword(s):  
Lymph Node ◽  
Dendritic Cell ◽  
B Cell ◽  
Cell Tumor ◽  
Secondary Malignancy ◽  
Small Lymphocytic Lymphoma ◽  
Dendritic Cell Sarcoma ◽  
Synchronous Neoplasm ◽  
Axillary Mass ◽  
Immunohistochemical Studies

Abstract A gradually enlarging axillary mass in a 79-year-old man was excised. The specimen was processed for light microscopy, immunohistochemical studies, and electron microscopy; gene rearrangement studies were also performed. A diagnosis of an interdigitating dendritic cell tumor of the lymph node and a B-cell small lymphocytic lymphoma occurring in the same anatomic location was made. We found that although rare cases of interdigitating dendritic cell tumor with an associated secondary malignancy have been described in the literature, to our knowledge, this is the first report of interdigitating dendritic cell tumor and synchronous neoplasm diagnosed at the same site. A possible relationship between the 2 disorders is also discussed.

Follicular Lymphoma in Staging Bone Marrow Specimens: Correlation of Histologic Findings With the Results of Flow Cytometry Immunophenotypic Analysis

2007 ◽  
Vol 131 (2) ◽  
pp. 282-287
Author(s):  
Dan Iancu ◽  
Suyang Hao ◽  
Pei Lin ◽  
S. Keith Anderson ◽  
Jeffrey L. Jorgensen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Bone Marrow Biopsy ◽  
Cell Population ◽  
Color Flow ◽  
Flow Cytometric Immunophenotyping ◽  
Histologic Evidence ◽  
Flow Cytometric ◽  
Biopsy Specimens

Abstract Context.—Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients. Objective.—To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients. Design.—Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates. Results.—Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was &lt;5% in 32 (17.1%), ≥5% and ≤25% in 102 (54.6%), &gt;25% and ≤50% in 27 (14.4%), and &gt;50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%). Conclusions.—Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients.

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