-
Cancer Science Sep 2023Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its...
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX-LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease-modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL-6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX-LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.
Topics: Humans; Methotrexate; Retrospective Studies; Tacrolimus; Arthritis, Rheumatoid; Antirheumatic Agents; Lymphoproliferative Disorders
PubMed: 37365854
DOI: 10.1111/cas.15894 -
Archives of Pathology & Laboratory... Jan 2018- The diagnosis of gastrointestinal lymphoproliferative disorders can be challenging because of the small size of biopsies and the wide spectrum of lymphoproliferative... (Review)
Review
CONTEXT
- The diagnosis of gastrointestinal lymphoproliferative disorders can be challenging because of the small size of biopsies and the wide spectrum of lymphoproliferative disorders that may be encountered.
OBJECTIVE
- To review the spectrum of lymphoproliferative disorders involving the gastrointestinal tract, highlighting potential pitfalls.
DATA SOURCES
- Peer-reviewed articles and clinical experience.
CONCLUSIONS
- Interpretation of lymphoid infiltrates in gastrointestinal biopsies requires synthesis of morphologic, immunophenotypic, molecular genetic, and clinical information. Knowledge of indolent lymphoproliferative disorders that may mimic aggressive lymphomas will help in preventing misdiagnoses.
Topics: Enteropathy-Associated T-Cell Lymphoma; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Killer Cells, Natural; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoproliferative Disorders
PubMed: 28829152
DOI: 10.5858/arpa.2016-0610-RA -
Cancer Medicine Oct 2021Epstein-Barr virus (EBV) is detected in a variety of B-cell lymphomas (BCLs) and B-cell lymphoproliferative disorders (B-LPDs). Immunodeficiency has been considered to... (Review)
Review
BACKGROUND
Epstein-Barr virus (EBV) is detected in a variety of B-cell lymphomas (BCLs) and B-cell lymphoproliferative disorders (B-LPDs). Immunodeficiency has been considered to play a key role in the pathogenesis of these diseases. In addition, immune escape of tumor cells may also contribute to the development of EBV BCLs and B-LPDs. The PD-1/PD-L1 pathway is particularly important for immune escape of tumor cells that contribute to development of lymphoma through suppression of cytotoxic T-cell function. We now consider PD-L1 immunohistochemistry (IHC) a very useful method for predicting whether tumor cells of lymphoid malignancies are characterized by the immune escape mechanism.
METHODS
We reviewed articles of EBV BCLs and B-LPDs from the perspective of immune escape and immunodeficiency, particularly focusing on PD-L1 IHC.
RESULTS
Based on PD-L1 IHC, we consider that EBV BCL and B-LPD can be classified into three types: "immunodeficiency", "immune escape", and "immunodeficiency + immune escape" type. The immunodeficiency type includes EBV diffuse large BCL (DLBCL) of the elderly, EBV sporadic Burkitt lymphoma, EBV mucocutaneous ulcer, and methotrexate (MTX)-associated B-LPD. The immune escape type includes EBV classic Hodgkin lymphoma (CHL) and EBV DLBCL of the young. The immunodeficiency + immune escape type includes CHL type MTX-associated LPD and a minor subset of EBV DLBCL of the elderly.
CONCLUSIONS
Recently, good results have been reported for immune check-point inhibitors in treating lymphoma. Lymphomas and LPDs characterized by immune escape are regarded as good candidates for PD1/PD-L1 blockade therapy. Therefore, from both the clinical and pathological perspective, we suggest that lymphoma diagnosis should be made considering immune escape and immunodeficiency.
Topics: Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Male; Middle Aged; Primary Immunodeficiency Diseases; Tumor Escape
PubMed: 34387382
DOI: 10.1002/cam4.4198 -
Dermatology (Basel, Switzerland) 2018The prompt identification of cutaneous lymphoproliferative disorders (CLD) has always been a challenge in dermatological practice, due to the rarity of this group of... (Review)
Review
The prompt identification of cutaneous lymphoproliferative disorders (CLD) has always been a challenge in dermatological practice, due to the rarity of this group of diseases, the heterogeneity in clinical presentation, and plenty of variants described in the literature so far. The strict cooperation between dermatologist and pathologist is the key element for the correct diagnosis of CLD deriving from the perfect integration of clinical and histopathological features. In this complex context, dermoscopy could play an adjuvant role in the achievement of the diagnosis, as it fits itself as the third diagnostic tool in the paraphernalia of the dermatologist between the clinical and histopathological examination. This review provides the state of art of dermoscopy of CLD.
Topics: Dermoscopy; Humans; Lymphoproliferative Disorders; Skin Neoplasms
PubMed: 30032152
DOI: 10.1159/000490412 -
The Journal of Dermatology Sep 2021Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare cutaneous disease associated with Epstein-Barr virus infection. We retrospectively analyzed the...
Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare cutaneous disease associated with Epstein-Barr virus infection. We retrospectively analyzed the clinical presentation, histopathological characteristics, and prognostic study of HV-LPD in 24 Chinese patients. All patients presented with recurrent papulovesicular and necrotic eruptions on the face, neck, and extremities, with 11 showing systemic symptoms. Twenty patients were diagnosed with HV-LPD in childhood (age < 18 years) and four in adulthood (age ≥ 18 years). The median age at diagnosis was 8.5 years old (range, 2-50). Histopathology revealed variably dense lymphocyte infiltration throughout the dermis. All cases were strongly positive for CD3 and Epstein-Barr encoding region based on in situ hybridization. Of 18 cases with a T-cell phenotype, 15 harbored monoclonal rearrangements in T-cell receptor (TCR) genes. Four cases with a natural killer cell phenotype carried polyclonal rearrangements in TCR genes. Among 24 patients, eight (33.3%) received chemotherapy, two (8.3%) allogeneic hematopoietic stem cell transplantation, and both are currently alive without disease. The median follow-up period was 24 months (range, 7-120) and 23 patients were available: 15 (62.5%) were alive, and eight (33.3%) had died. Fourteen cases had a relapse of disease and three developed lymphoma within 24 months of diagnosis. The mean survival time of childhood-onset patients was longer than that of adult-onset patients (36.4 vs. 20.8 months). In summary, the wide clinical course and representative presentation of cases in our center reflect the pedigree characteristics of HV-LPD. Allogeneic hematopoietic stem cell transplantation should be a preferred choice for relapse and refractory patients due to the poor effect of chemotherapy. Adult-onset and high serum EBV DNA loads may indicate an increased risk of aggressive disease in patients with HV-LPD.
Topics: Adolescent; Adult; Child; China; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Hydroa Vacciniforme; Lymphoma; Lymphoproliferative Disorders; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies
PubMed: 33982815
DOI: 10.1111/1346-8138.15944 -
Journal of Clinical and Experimental... 2019Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) with a T- or NK-cell phenotype are markedly rare, with only a limited number of... (Review)
Review
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) with a T- or NK-cell phenotype are markedly rare, with only a limited number of cases having been reported thus far. Methotrexate (MTX) is the most common agent used for OIIA-LPD patients, and 43 cases of MTX-associated T-LPDs (MTX T-LPDs) and five cases of MTX-associated NK/T-LPDs (MTX NK-LPDs) have been described. In addition to MTX T-LPDs and MTX NK/T-LPDs, T-LPD and NK/T-LPDs have been reported in patients receiving other immunosuppressive agents such as thiopurines, TNF antagonists, and cyclosporine. Hepatosplenic T-cell lymphoma (HSTL) is specifically associated with iatrogenic immunodeficiency, and 10% of HSTL cases develop in patients receiving thiopurines and/or TNF antagonists for inflammatory bowel disease (IBD). In this review, we focused on MTX T-LPD, MTX NK/T-LPD, and HSTL in patients with IBD. These T- and NK/T-cell associated OIIA-LPDs are the most common in daily medical practice.
Topics: Animals; Humans; Iatrogenic Disease; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoproliferative Disorders; Methotrexate; Natural Killer T-Cells; T-Lymphocytes
PubMed: 31257346
DOI: 10.3960/jslrt.19013 -
Current Oncology (Toronto, Ont.) Nov 2021Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only... (Review)
Review
Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only involvement of spleen and hilar lymph nodes. In contrast, secondary low-grade B-cell lymphomas in the spleen, such as follicular lymphomas (FL), lymphoplasmacytic lymphoma and chronic lymphocytic leukemia/ small lymphocytic lymphoma, particularly as part of advanced stage disease, are more common. Indolent B cell lymphomas expressing CD10 almost always represent FL, which in its primary splenic form is the focus of this review. Primary splenic follicular lymphoma (PSFL) is exceedingly infrequent. This type of lymphoproliferative disorder is understudied and, in most cases, clinically characterized by splenomegaly or cytopenias related to hypersplenism. The diagnosis requires correlation of histopathology of spleen, blood and/or bone marrow with the correct immunophenotype (determined by flow cytometry and/or immunohistochemistry) and if necessary, additional molecular profiling. Management of this incurable disease is evolving, and splenectomy remains the mainstream treatment for stage I PSFL.
Topics: Humans; Immunohistochemistry; Immunophenotyping; Lymphoma, B-Cell; Lymphoma, Follicular; Spleen
PubMed: 34898578
DOI: 10.3390/curroncol28060407 -
Rheumatology International Feb 2015Primary Sjögren's syndrome is an autoimmune disorder with external exocrine glands dysfunction and multiorgan involvement. The pathogenesis of primary Sjogren's... (Review)
Review
Primary Sjögren's syndrome is an autoimmune disorder with external exocrine glands dysfunction and multiorgan involvement. The pathogenesis of primary Sjogren's syndrome is still unclear; however, our knowledge of the involvement of different cells (e.g., B and T cells, macrophages and dendritic cells) and pathways (BAFF/APRIL and interferons) leading to the development of autoimmunity is continually expanding. For clinicians, the most frequent symptoms are dryness of eyes and mouth, but often the patients have musculoskeletal symptoms and systemic manifestations. However, the increased risk of lymphoproliferative disorders in this group of patients, most commonly B-cell marginal zone lymphoma, is particularly important. Recent separation of IgG4-related diseases and attempts to create further diagnostic criteria for pSS testify to the difficulties, and at the same time a large interest, in understanding the disease so as to allow the effective treatment. This article draws attention to the problems faced by the clinician wishing to securely identify pSS by using accurate laboratory biomarkers and useful imaging tools and predict the development of complications associated with this, still not fully understood, autoimmune disease.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Humans; Immunoglobulin G; Lymphoproliferative Disorders; Risk Factors; Sjogren's Syndrome
PubMed: 24985362
DOI: 10.1007/s00296-014-3072-5 -
Cytometry. Part B, Clinical Cytometry Mar 2019This article provides an overview of the role of flow cytometry in the diagnosis, prognosis, and follow-up of T and NK-cell lymphoproliferative disorders. For each... (Review)
Review
This article provides an overview of the role of flow cytometry in the diagnosis, prognosis, and follow-up of T and NK-cell lymphoproliferative disorders. For each category, we will briefly discuss the immunophenotypic features of normal T and NK cells, and address technical issues in flow cytometry, the approach to diagnosis in various contexts, pitfalls in interpretation, and its use in follow-up and post-therapy management. In addition to reviewing the diagnostic, prognostic, and therapeutic utility of flow cytometric immunophenotyping in several of specific T and NK cell entities, we will also cover some of the new immunophenotypic markers. Furthermore, we will touch upon incorporation of flow cytometry in the final diagnosis, including correlation with other ancillary tests. © 2019 International Clinical Cytometry Society.
Topics: Flow Cytometry; Humans; Immunophenotyping; Killer Cells, Natural; Lymphoproliferative Disorders; T-Lymphocytes
PubMed: 30729667
DOI: 10.1002/cyto.b.21768 -
Journal of Dermatological Science Aug 2020Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) encompasses a rare group of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases.
BACKGROUND
Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) encompasses a rare group of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases.
OBJECTIVE
To define the clinical and pathologic characteristics of HVLPD and to identify mutant genes that may be related to the development of HVLPD.
METHODS
Clinical data and archived formalin-fixed, paraffin-embedded tissue were obtained from 19 patients. Specimens were analyzed by immunohistochemistry and in situ hybridization to detect EBV-encoded RNA (EBER1/2) and for T cell receptor (TCR) gene rearrangements. Whole-exome sequencing (WES) analysis was also performed in this study.
RESULTS
Thirteen patients survived between 3-58 months (median, 21 months) during the follow-up. Six patients who were almost adults (>15 years old) and died of the disease presented with facial edema. Lactate dehydrogenase (LDH) levels were elevated, and the TCR gene rearrangement test was positive more frequently in the patients who died. Compared with Chinese patients in a similar previous report, our patients had significantly higher proliferation (in all cases, the Ki-67 index was greater than 10 %) and a more aggressive clinical course. Moreover, after WES and Sanger verification, STAT3, IKBKB, ELF3, CHD7, KMT2D, ELK1, RARB and HPGDS were screened out in our patients.
CONCLUSIONS
HVLPD refers to a heterogeneous group of cutaneous lymphoproliferative diseases with different clinical and pathological features that affect patient outcomes. Gene mutations may be correlated with the development of HVLPD, and our study may provide new therapeutic targets for HVLPD.
Topics: Adolescent; Adult; Biomarkers; Cell Proliferation; Child; Child, Preschool; China; DNA Mutational Analysis; Epstein-Barr Virus Infections; Female; Follow-Up Studies; Herpesvirus 4, Human; Humans; Hydroa Vacciniforme; Lymphoproliferative Disorders; Male; Middle Aged; Mutation; Photography; RNA, Viral; Retrospective Studies; Skin; Exome Sequencing; Young Adult
PubMed: 32682634
DOI: 10.1016/j.jdermsci.2020.06.013