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Keywords = lymphoproliferative neoplasm

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26 pages, 2610 KiB  
Review
Immunosuppressants/Immunomodulators and Malignancy
by Norishige Iizuka, Yoshihiko Hoshida, Atsuko Tsujii Miyamoto, Hotaka Shigyo, Akira Nishigaichi, Gensuke Okamura and Shiro Ohshima
J. Clin. Med. 2025, 14(14), 5160; https://doi.org/10.3390/jcm14145160 - 21 Jul 2025
Viewed by 1021
Abstract
Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a [...] Read more.
Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a high incidence of virus-associated cancers, and are reversible in some cases. Notably, immunosuppressive agents influence the frequency and type of malignancies, as well as their clinicopathological features. Organ transplant recipients receive long-term immunosuppressants to prevent acute rejection. Post-transplant malignancies vary depending on the type of drug administered before the onset of these diseases. Patients with rheumatoid arthritis (RA) are treated with long-term immunosuppressive medications, such as methotrexate (MTX). MTX is widely recognized as being associated with a specific type of lymphoproliferative disorder (LPD), known as MTX-associated LPD. Our recent report indicated that the clinicopathological features of rheumatoid arthritis-associated lymphoproliferative disorder (RA-LPD) also vary based on the other anti-RA agents used, such as tacrolimus and tumor necrosis factor inhibitors. Therefore, the clinicopathological characteristics of post-transplant LPD and RA-LPD evolve alongside the changes in the immunosuppressants/immunomodulators administered. Understanding the various characteristics and time trends of immunosuppressive neoplasms, particularly LPDs, in relation to different immunosuppressant/immunomodulator medications is highly valuable in clinical practice. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)
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20 pages, 3018 KiB  
Review
A Review of KSHV/HHV8-Associated Neoplasms and Related Lymphoproliferative Lesions
by Jamie Rigney, Kevin Zhang, Michael Greas and Yan Liu
Lymphatics 2025, 3(3), 20; https://doi.org/10.3390/lymphatics3030020 - 15 Jul 2025
Viewed by 427
Abstract
There has been extensive research on the KSHV/HHV8 virus, which has led to a better understanding of viral transmission, pathogenesis, viral-driven lymphoid proliferation, neoplastic transformation, and how we might combat these processes clinically. On an extensive review of the literature, only two true [...] Read more.
There has been extensive research on the KSHV/HHV8 virus, which has led to a better understanding of viral transmission, pathogenesis, viral-driven lymphoid proliferation, neoplastic transformation, and how we might combat these processes clinically. On an extensive review of the literature, only two true KSHV/HHV8-positive lymphoid neoplasms are described: primary effusion lymphoma (PEL), which can also present as solid or extracavitary primary effusion lymphoma (EC-PEL) and diffuse large B-cell lymphoma (DLBCL). Two lymphoproliferative disorders have also been described, and while they are not true monotypic neoplasms, these lesions can transform into neoplasms: KSHV/HHV8-positive germinotropic lymphoproliferative disorder (GLPD) and multicentric Castleman disease (MCD). This review provides a somewhat concise overview of information related to KSHV/HHV8-positive lymphoid neoplasms and pertinent associated lymphoproliferative lesions. Full article
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25 pages, 1453 KiB  
Review
Molecular Mechanisms in the Transformation from Indolent to Aggressive B Cell Malignancies
by Nawar Maher, Samir Mouhssine, Bassam Francis Matti, Alaa Fadhil Alwan and Gianluca Gaidano
Cancers 2025, 17(5), 907; https://doi.org/10.3390/cancers17050907 - 6 Mar 2025
Cited by 3 | Viewed by 1547
Abstract
Histological transformation (HT) into aggressive lymphoma is a turning point in a significant fraction of patients affected by indolent lymphoproliferative neoplasms, namely, chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphomas (MZLs), and lymphoplasmacytic lymphoma (LPL) [...] Full article
(This article belongs to the Special Issue Oncogenesis of Lymphoma)
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10 pages, 770 KiB  
Article
Inflammatory Markers Significantly Increased in Patients Treated with Obinotuzumab for Lymphoproliferative Diseases
by Krzysztof Gawronski, Nadia Hussein and Piotr Rzepecki
J. Clin. Med. 2024, 13(23), 7146; https://doi.org/10.3390/jcm13237146 - 26 Nov 2024
Viewed by 863
Abstract
Background: The purpose of this study was to analyze the behaviors of inflammatory markers, such as procalcitonin and C-reactive protein (CRP), during treatment with obinotuzumab (an anti-CD20 antibody). Methods: Our non-randomized observational study prospectively evaluated a cohort of 22 adult patients [...] Read more.
Background: The purpose of this study was to analyze the behaviors of inflammatory markers, such as procalcitonin and C-reactive protein (CRP), during treatment with obinotuzumab (an anti-CD20 antibody). Methods: Our non-randomized observational study prospectively evaluated a cohort of 22 adult patients with lymphoproliferative neoplasms, chronic lymphocytic leukemia (CLL), and follicular lymphoma (FL) with indications for obinotuzumab therapy. Results: All patients had their blood drawn to determine blood counts, CRP, and procalcitonin, as well as body temperature measurements and blood cultures performed for bacterial infections on day 0 before administration of the anti-CD20 antibody. Subsequently, on days 1 to 7 after administration, blood was drawn daily at a fixed time of 8:00 a.m. for blood counts and CRP and PCT values, and blood cultures were performed. In addition, on days 1 to 7, body temperature was measured at fixed times (i.e., 8:00 a.m. and 8:00 p.m.). In all of these patients, significant increases in inflammatory markers, such as CRP and procalcitonin, were observed shortly after drug infusion. There was a statistically significant change in the serum PCT concentration (p < 0.0001), which significantly increased on days 1 to 4 compared to the initial measurement 0. Conclusions: The increases in inflammatory markers shortly after obinotuzumab (anti-CD20 antibody) administration can be significantly high but are most often not related to the onset of infection and do not lead to any ill consequences in the treatment of lymphoproliferative disease. Full article
(This article belongs to the Special Issue Hematologic Malignancies: Treatment Strategies and Future Challenges)
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18 pages, 336 KiB  
Article
Cluster of Differentiation Markers and Human Leukocyte Antigen Expression in Chronic Lymphocytic Leukemia Patients: Correlations and Clinical Relevance
by Maria Tizu, Bogdan Calenic, Alexandra-Elena Constantinescu, Alexandru Adrian Bratei, Razvan Antonio Stoia, Mihnea Catalin-Gabriel Popa and Ileana Constantinescu
Curr. Issues Mol. Biol. 2024, 46(9), 10008-10025; https://doi.org/10.3390/cimb46090598 - 11 Sep 2024
Viewed by 2715
Abstract
Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD79b, CD45, CD23, CD22 and CD81 [...] Read more.
Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD79b, CD45, CD23, CD22 and CD81 serve as reliable prognostic indicators in CLL as well as the human leukocyte antigen (HLA) with its well-documented associations with various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Although it is one of the most prevalent neoplasms, there is a need for biomarkers that can improve survival. This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing was performed for HLA typing. The results indicate that several CD markers are statistically associated with different HLA alleles, specifically CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01. In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL. Full article
(This article belongs to the Section Molecular Medicine)
8 pages, 18526 KiB  
Case Report
Atypical Plasma Cell Leukemia Mistaken for Acute Leukemia: A Case Report
by Irena Seili-Bekafigo, Emina Torlakovic, Tajana Grenko Malnar, Marija Stanić Damić, Željko Prka, Koviljka Matušan Ilijaš and Ita Hadžisejdić
Medicina 2024, 60(8), 1351; https://doi.org/10.3390/medicina60081351 - 20 Aug 2024
Viewed by 2120
Abstract
The patient we present here had many clinical, morphological, and laboratory findings characteristic of acute leukemia. During the course of the disease, the diagnosis changed from acute leukemia to chronic small B-cell lymphoproliferative disease, a blastoid variant of mantle cell lymphoma, and finally [...] Read more.
The patient we present here had many clinical, morphological, and laboratory findings characteristic of acute leukemia. During the course of the disease, the diagnosis changed from acute leukemia to chronic small B-cell lymphoproliferative disease, a blastoid variant of mantle cell lymphoma, and finally to atypical plasma cell leukemia. Atypical plasma cell leukemia is a rare condition with aggressive biological behavior. Our patient relapsed a short time after achieving complete remission, in spite of aggressive therapy and autologous stem cell transplantation. During relapse, it was possible to morphologically identify malignant cells as being of plasma cell origin, although immature and atypical. Atypical plasma cell leukemia presents a diagnostic challenge as it may mimic other neoplasms both morphologically and clinically. It is also recognized that plasma cell neoplasm immunophenotype may not be entirely specific for its lineage where common diagnostic biomarkers are applied by immunohistochemistry or flow cytometry. Where this is the case, only focused investigation for plasma cell lineage will be more informative. This patient has unusual clinical presentation, a nondescript morphology of the circulating plasma cells, as well as an immunophenotype, detected by the initial panels used for flow cytometry and immunohistochemistry, that was not entirely specific for plasma cells. Such cases present a good reminder of the diagnostic complexity of atypical plasma cell leukemia and emphasize that plasma cell differentiation needs to be interrogated in cases where the initial work-up shows unusual results. Full article
(This article belongs to the Special Issue Cutting-Edge Research in Relapsed and Refractory Multiple Myeloma)
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11 pages, 4098 KiB  
Article
Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms
by Danijela Lekovic, Jelena Ivanovic, Tatjana Terzic, Maja Perunicic Jovanovic, Marija Dencic Fekete, Jelica Jovanovic, Isidora Arsenovic, Vojin Vukovic, Jelena Bila, Andrija Bogdanovic and Darko Antic
J. Clin. Med. 2024, 13(6), 1816; https://doi.org/10.3390/jcm13061816 - 21 Mar 2024
Viewed by 1924
Abstract
Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients [...] Read more.
Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22–69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk. Full article
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27 pages, 1251 KiB  
Review
Rare Hematologic Malignancies and Pre-Leukemic Entities in Children and Adolescents Young Adults
by Amber Brown and Sandeep Batra
Cancers 2024, 16(5), 997; https://doi.org/10.3390/cancers16050997 - 29 Feb 2024
Cited by 1 | Viewed by 2372
Abstract
There are a variety of rare hematologic malignancies and germline predispositions syndromes that occur in children and adolescent young adults (AYAs). These entities are important to recognize, as an accurate diagnosis is essential for risk assessment, prognostication, and treatment. This descriptive review summarizes [...] Read more.
There are a variety of rare hematologic malignancies and germline predispositions syndromes that occur in children and adolescent young adults (AYAs). These entities are important to recognize, as an accurate diagnosis is essential for risk assessment, prognostication, and treatment. This descriptive review summarizes rare hematologic malignancies, myelodysplastic neoplasms, and germline predispositions syndromes that occur in children and AYAs. We discuss the unique biology, characteristic genomic aberrations, rare presentations, diagnostic challenges, novel treatments, and outcomes associated with these rare entities. Full article
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13 pages, 2629 KiB  
Review
Understanding the Role of Bispecific Antibodies in the Management of B-Cell Non-Hodgkin Lymphoma: A New Immunotherapy That Is Here to Stay
by Stanislav Ivanov, Meri Muminovic and Jose Sandoval-Sus
Lymphatics 2023, 1(3), 244-256; https://doi.org/10.3390/lymphatics1030015 - 6 Oct 2023
Cited by 1 | Viewed by 2436
Abstract
Non-Hodgkin lymphomas (NHLs) represent a diverse group of hematologic malignancies derived from various cells. B-cell NHLs represent the largest fraction of lymphomas diagnosed and treated in the United States. Standard chemo-immunotherapies with rituximab and multiagent cytotoxic regimens have proven to be effective in [...] Read more.
Non-Hodgkin lymphomas (NHLs) represent a diverse group of hematologic malignancies derived from various cells. B-cell NHLs represent the largest fraction of lymphomas diagnosed and treated in the United States. Standard chemo-immunotherapies with rituximab and multiagent cytotoxic regimens have proven to be effective in the management of these lymphoproliferative neoplasms; nonetheless, a considerable fraction of patients still experience relapse or have treatment-refractory disease. Therapeutic advances using novel immunotherapeutic agents as well as cell-based treatments, such as chimeric antigen receptor (CAR) T-cell therapies, have improved the outcomes of relapsed/refractory (R/R) B-cell NHL. Most of these new treatment strategies are not curative and most patients succumb to R/R disease, leaving this population with an unmet need for effective and well-tolerated therapeutic options. One of these up-and-coming options are bispecific antibodies (BsAb), either as single agent or in combination with other medications. Conclusion: BsAbs offer a novel “off the shelf” chemotherapy-free approach in the management of R/R B-cell NHL. Advancements in antibody construct design along with improved safety profile and clinical effectiveness of the most recent BsAbs suggest that these agents are a promising new option in the management of R/R B-cell NHL. Full article
(This article belongs to the Collection Lymphomas)
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20 pages, 10966 KiB  
Article
Unusual Presentation of SET::NUP214-Associated Concomitant Hematological Neoplasm in a Child—Diagnostic and Treatment Struggle
by Yaroslav Menchits, Tatiana Salimova, Alexander Komkov, Dmitry Abramov, Tatiana Konyukhova, Ruslan Abasov, Elena Raykina, Albert Itov, Marina Gaskova, Aleksandra Borkovskaia, Anna Kazakova, Olga Soldatkina, Svetlana Kashpor, Alexandra Semchenkova, Alexander Popov, Galina Novichkova, Yulia Olshanskaya, Alexey Maschan and Elena Zerkalenkova
Int. J. Mol. Sci. 2023, 24(19), 14451; https://doi.org/10.3390/ijms241914451 - 22 Sep 2023
Cited by 2 | Viewed by 2321
Abstract
Simultaneous multilineage hematologic malignancies are uncommon and associated with poorer prognosis than single-lineage leukemia or lymphoma. Here, we describe a concomitant malignant neoplasm in a 4-year-old boy. The child presented with massive lymphoproliferative syndrome, nasal breathing difficulties, and snoring. Morphological, immunocytochemical, and flow [...] Read more.
Simultaneous multilineage hematologic malignancies are uncommon and associated with poorer prognosis than single-lineage leukemia or lymphoma. Here, we describe a concomitant malignant neoplasm in a 4-year-old boy. The child presented with massive lymphoproliferative syndrome, nasal breathing difficulties, and snoring. Morphological, immunocytochemical, and flow cytometry diagnostics showed coexistence of acute myeloid leukemia (AML) and peripheral T-cell lymphoma (PTCL). Molecular examination revealed a rare t(9;9)(q34;q34)/SET::NUP214 translocation as well as common TCR clonal rearrangements in both the bone marrow and lymph nodes. The disease showed primary refractoriness to both lymphoid and myeloid high-dose chemotherapy as well as combined targeted therapy (trametinib + ruxolitinib). Hence, HSCT was performed, and the patient has since been in complete remission for over a year. This observation highlights the importance of molecular techniques for determining the united nature of complex SET::NUP214-positive malignant neoplasms arising from precursor cells with high lineage plasticity. Full article
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20 pages, 3685 KiB  
Review
T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment
by Marc Gutierrez, Patrick Bladek, Busra Goksu, Carlos Murga-Zamalloa, Dale Bixby and Ryan Wilcox
Int. J. Mol. Sci. 2023, 24(15), 12106; https://doi.org/10.3390/ijms241512106 - 28 Jul 2023
Cited by 9 | Viewed by 8154
Abstract
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. [...] Read more.
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. In 2019, the T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis, staging, and assessment of response to treatment of T-PLL with the goal of harmonizing research efforts and supporting clinical decision-making. T-PLL pathogenesis is commonly driven by T-cell leukemia 1 (TCL1) overexpression and ATM loss, genetic alterations that are incorporated into the TPLL-ISG diagnostic criteria. The cooperativity between TCL1 family members and ATM is seemingly unique to T-PLL across the spectrum of T-cell neoplasms. The role of the T-cell receptor, its downstream kinases, and JAK/STAT signaling are also emerging themes in disease pathogenesis and have obvious therapeutic implications. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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23 pages, 797 KiB  
Review
Tumor-Associated Macrophages in Multiple Myeloma: Key Role in Disease Biology and Potential Therapeutic Implications
by Emanuele Cencini, Anna Sicuranza, Sara Ciofini, Alberto Fabbri, Monica Bocchia and Alessandro Gozzetti
Curr. Oncol. 2023, 30(7), 6111-6133; https://doi.org/10.3390/curroncol30070455 - 25 Jun 2023
Cited by 16 | Viewed by 3806
Abstract
Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk [...] Read more.
Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk between these cells and the MM tumor cells. Tumor-associated macrophages (TAM) have an important role in the MM pathogenesis, since they could promote plasma cells proliferation and angiogenesis, further supporting MM immune evasion and progression. TAM are polarized towards M1 (classically activated, antitumor activity) and M2 (alternatively activated, pro-tumor activity) subtypes. Many studies demonstrated a correlation between TAM, disease progression, drug-resistance and reduced survival in lymphoproliferative neoplasms, including MM. MM plasma cells in vitro could favor an M2 TAM polarization. Moreover, a possible correlation between the pro-tumor effect of M2 TAM and a reduced sensitivity to proteasome inhibitors and immunomodulatory drugs was hypothesized. Several clinical studies confirmed CD68/CD163 double-positive M2 TAM were associated with increased microvessel density, chemoresistance and reduced survival, independently of the MM stage. This review provided an overview of the biology and clinical relevance of TAM in MM, as well as a comprehensive evaluation of a potential TAM-targeted immunotherapy. Full article
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13 pages, 271 KiB  
Article
Assessment of Metabolic Syndrome and Kidney and Heart Function in Childhood Cancer Survivors
by Aleksandra Janecka, Joanna Stefanowicz, Anna Owczarzak, Marek Tomaszewski, Tomasz Batko and Ninela Irga-Jaworska
Children 2023, 10(6), 1073; https://doi.org/10.3390/children10061073 - 18 Jun 2023
Cited by 1 | Viewed by 2083
Abstract
Background: The survivors of childhood cancer suffer from a number of long-term side effects. These include atherosclerosis and cardiovascular diseases (CVDs) that develop earlier in adulthood than in the rest of the population. The aim of this study was to identify prognostic factors [...] Read more.
Background: The survivors of childhood cancer suffer from a number of long-term side effects. These include atherosclerosis and cardiovascular diseases (CVDs) that develop earlier in adulthood than in the rest of the population. The aim of this study was to identify prognostic factors of developing atherosclerosis before the development of symptomatic CVD. Methods: A total of 141 children that were 7–18 years old were examined; there were 116 survivors of childhood malignancies (hematopoietic and lymphoproliferative malignancies—52; neuroblastoma—22; Wilms tumor—24; other solid tumors—18) and 25 healthy controls. Anthropometric measurements, blood pressure measurements, ultrasonography of the abdomen, echocardiography, and laboratory tests were performed. Results: There were no significant differences in gender distribution, time from the end of the treatment, weight, BMI, prevalence of central obesity, blood pressure and resistive index of the renal arteries, lipid profile, or glucose and fibrinogen levels. Patients with solid tumors had a significantly lower height and worse renal function. Patients with hematological malignancies significantly presented the lowest shortening fraction of the left ventricle. The salusin β levels were significantly higher in the control group than among the patients. Conclusions: The type and severity of side effects are closely related to the type of neoplasm and the treatment that has been undergone. Careful observation and regular follow-up are necessary. Full article
20 pages, 7374 KiB  
Article
Spontaneous EBV-Reactivation during B Cell Differentiation as a Model for Polymorphic EBV-Driven Lymphoproliferation
by Matthew A. Care, Sophie Stephenson, Roger Owen, Gina M. Doody and Reuben M. Tooze
Cancers 2023, 15(12), 3083; https://doi.org/10.3390/cancers15123083 - 7 Jun 2023
Cited by 1 | Viewed by 2455
Abstract
Epstein-Barr virus (EBV)-driven B cell neoplasms arise from the reactivation of latently infected B cells. In a subset of patients, EBV was seen to drive a polymorphous lymphoproliferative disorder (LPD) in which B cell differentiation was retained. In this work, spontaneous EBV reactivation [...] Read more.
Epstein-Barr virus (EBV)-driven B cell neoplasms arise from the reactivation of latently infected B cells. In a subset of patients, EBV was seen to drive a polymorphous lymphoproliferative disorder (LPD) in which B cell differentiation was retained. In this work, spontaneous EBV reactivation following B cell mitogen stimulation was shown to provide a potential model of polymorphic EBV-driven LPD. Here, we developed an in vitro model of plasma cell (PC) differentiation from peripheral blood memory B cells. To assess the frequency and phenotypes of EBV-associated populations derived during differentiation, we analysed eight differentiations during the PC stage with a targeted single-cell gene expression panel. We identified subpopulations of EBV-gene expressing cells with PC and/or B cell expression features in differentiations from all tested donors. EBV-associated cells varied in frequency, ranging from 3–28% of cells. Most EBV-associated cells expressed PC genes such as XBP1 or MZB1, and in all samples these included a quiescent PC fraction that lacked cell a cycle gene expression. With increasing EBV-associated cells, populations with B cell features became prominent, co-expressing a germinal centre (GC) and activating B cell gene patterns. The presence of highly proliferative EBV-associated cells was linked to retained MS4A1/CD20 expression and IGHM and IGHD co-expression, while IGHM class-switched cells were enriched in quiescent PC fractions. Thus, patterns of gene expression in primary EBV reactivation were shown to include features related to GC B cells, which was also observed in EBV-transformed lymphoblastoid cell lines. This suggests a particular association between spontaneously developing EBV-expansions and IgM+ IgD+ non-switched B cells. Full article
(This article belongs to the Special Issue Epstein-Barr Virus-Associated Cancers: From Pathogenesis to Treatment)
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14 pages, 1925 KiB  
Article
Clinical and Histopathological Features of an Italian Monocentric Series of Primary Small Bowel T-Cell Lymphomas
by Marco Lucioni, Sara Fraticelli, Giovanni Santacroce, Arturo Bonometti, Nicola Aronico, Roberta Sciarra, Marco Vincenzo Lenti, Paola Ilaria Bianchi, Giuseppe Neri, Monica Feltri, Benedetto Neri, Giuseppina Ferrario, Roberta Riboni, Gino Roberto Corazza, Alessandro Vanoli, Luca Arcaini, Marco Paulli and Antonio Di Sabatino
Cancers 2023, 15(10), 2743; https://doi.org/10.3390/cancers15102743 - 13 May 2023
Cited by 10 | Viewed by 2116
Abstract
The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical–pathological profile of a series [...] Read more.
The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical–pathological profile of a series of patients affected by intestinal T-cell lymphomas (ITCL) and possibly define hallmarks of these neoplasms. A total of 28 patients were included: 17 enteropathy-associated T-cell lymphomas (EATL), 5 monomorphic epitheliotropic T-cell lymphomas (MEITL), 3 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (ITCLDGT), and 3 intestinal T-cell lymphomas not otherwise specified (ITCL-NOS). Celiac disease (CD) was diagnosed in around 70% of cases. Diagnosis of EATL showed a significant correlation with CD30 expression, whereas MEITL with angiotropism and CD56 positivity. ITCLDGT cases showed plasma cells infiltration. Peripheral lymphocytosis, the absence of a previous diagnosis of CD, an advanced Lugano clinical stage, and the histological subtype ITCL-NOS were significantly associated with worse survival at multivariate analysis. Our findings about the epidemiological, clinical, and histopathological features of ITCL were in line with the current knowledge. Reliable prognostic tools for these neoplasms are still lacking but according to our results lymphocytosis, diagnosis of CD, Lugano clinical stage, and histological subtype should be considered for patient stratification. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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