Type Of Lymphoma Research Articles

Primary colon lymphomas: An analysis of our experience over the last 18 years.

Colon lymphoma is a rare type of gastrointestinal lymphoma and represents 0.2% to -1.2% of all primary colon cancers. This study aimed to retrospectively examine the general characteristics, treatment methods, and survival characteristics of patients with colon lymphoma who were followed-up at our center. This retrospective study included patients diagnosed with colon lymphoma who were followed up at Ankara Numune Training and Research Hospital and Ankara Bilkent City Hospital between December 2005 and June 2023. Clinicopathological features, radiological findings, treatments, and modalities of patients were obtained from their medical records. Fourteen patients with primary colon lymphoma were included in the study. Thirteen patients (92.9%) were diagnosed with diffuse large B-cell lymphoma. The median age of the patients was 55 (28-84) years. The tumor location was the terminal ileum/cecum in 50% of the patients. At the time of diagnosis, 10 patients (7 with stage 1E-2E disease, 2 with stage 3E disease, and 1 with stage 4E disease due to tumor obstruction) underwent surgery. Twelve patients received chemotherapy (6 patients as adjuvant and 6 patients as first-line treatment). The median overall survival (OS) was 10 years (0.1-21.5) years, the 5-year median OS was 71%, and the 10-year median OS was 53%. Primary colon lymphoma is a rare disease and its optimal treatment is not clearly defined. The primary treatment for primary colon lymphoma is a combination of surgery and chemotherapy. A clear consensus on the treatment can be established through prospective studies.

The causal relationship between gut microbiota and lymphoma: a two-sample Mendelian randomization study

BackgroundPrevious studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of ambiguity.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between gut microbiota and five types of lymphoma. The research drew upon microbiome data from a research project of 14,306 participants and lymphoma data encompassing 324,650 cases. Single-nucleotide polymorphisms were meticulously chosen as instrumental variables according to multiple stringent criteria. Five MR methodologies, including the inverse variance weighted approach, were utilized to assess the direct causal impact between the microbial exposures and lymphoma outcomes. Moreover, sensitivity analyses were carried out to robustly scrutinize and validate the potential presence of heterogeneity and pleiotropy, thereby ensuring the reliability and accuracy.ResultsWe discerned 38 potential causal associations linking genetic predispositions within the gut microbiome to the development of lymphoma. A few of the more significant results are as follows: Genus Coprobacter (OR = 0.619, 95% CI 0.438–0.873, P = 0.006) demonstrated a potentially protective effect against Hodgkin’s lymphoma (HL). Genus Alistipes (OR = 0.473, 95% CI 0.278–0.807, P = 0.006) was a protective factor for diffuse large B-cell lymphoma. Genus Ruminococcaceae (OR = 0.541, 95% CI 0.341–0.857, P = 0.009) exhibited suggestive protective effects against follicular lymphoma. Genus LachnospiraceaeUCG001 (OR = 0.354, 95% CI 0.198–0.631, P = 0.0004) showed protective properties against T/NK cell lymphoma. The Q test indicated an absence of heterogeneity, and the MR-Egger test did not show significant horizontal polytropy. Furthermore, the leave-one-out analysis failed to identify any SNP that exerted a substantial influence on the overall results.ConclusionOur study elucidates a definitive causal link between gut microbiota and lymphoma development, pinpointing specific microbial taxa with potential causative roles in lymphomagenesis, as well as identifying probiotic candidates that may impact disease progression, which provide new ideas for possible therapeutic approaches to lymphoma and clues to the pathogenesis of lymphoma.

Skin-directed therapy and biologic response modifiers in mycosis fungoides

The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination.

Assessment of Native Myocardial T1 Mapping for Early Detection of Anthracycline-Induced Cardiotoxicity in Patients with Cancer: a Systematic Review and Meta-analysis.

Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Qtest, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.

Genomic landscape and distinct molecular subtypes of primary testicular lymphoma.

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.

A case of methotrexate-related lymphoproliferative disease showing multiple liver lesions in a patient with rheumatoid arthritis.

A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis.

Solitary large malignant lymphoma in the head and neck region

Solitary large malignant lymphoma in the head and neck region

Pyroptotic macrophages promote proliferation and chemotherapy resistance of peripheral T-cell lymphoma via TLR4 signaling pathway.

Peripheral T-cell lymphoma (PTCL) is a highly aggressive type of non-Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. Invitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL-18. Upregulated TLR4 activated its downstream NF-κB anti-apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF-κB anti-apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In-depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.

Bioaccessibility of bioactive compounds present in Persea americana Mill. seed ingredient during oral-gastric digestion with antibacterial capacity against Helicobacter pylori

In ancient Mexican cultures, the Persea americana Mill seed has been used against gastrointestinal diseases, due to high concentrations of bioactive compounds. According to Traditional Mexican Medicine, P. americana seed aqueous infusion is used against roundworms, intestinal worms, parasites, and gastrointestinal problems, in a dose taken over three or four days. In addition, Mexican Society of Natural History indicates the traditional use of P. americana seed powder as an antiparasitic, and antibacterial (MTM, 2009). On the other hand, Helicobacter pylori infection is a factor associated with the development of gastric disease, peptic ulcers as well as some types of gastric lymphomas and gastric cancer in humans; in this way is necessary scientific evidence about P. americana seed effect in gastrointestinal disease. The work aimed to evaluate bioactive compounds bioaccessibility and antimicrobial potential against Helicobacter pylori during oral-gastric digestion in vitro of food ingredient from Persea americana Mill. seed and elucidate the possible action mechanism using in silico tools. Initially, P. americana seed oil and aqueous extract of P. americana seed were obtained using ultrasound and maceration respectively, and the food ingredient from P. americana seed was obtained. The samples underwent oral-gastric digestions by the INFOGEST method, to continue identifying and quantifying the bioactive compounds by HPLC-DAD and GC-MS. The anti-Helicobacter pylori activity determination were used fourteen Helicobacter pylori clinical strains and reference strains by Susceptibility testing by Minimal Inhibition Concentration, Kinetics of Growth Inhibition of H. pylori, Urease Inhibitory Kinetic. Finally, to elucidate a possible action mechanism used in silico tools (Software AutoDock 4.2.6 and BioVia Discovery v.19.1.0.1.18287). The lipophilic fraction of P. americana seed detected oleic acid, linoleic acid, and avocadenofuran compounds, and the phenolic fraction showed the presence of catechin, rutin, ellagic, and chlorogenic acid, among others. Phenolic compounds conformational changes during oral-gastric digestion due to mechanical and acid hydrolysis, while lipophilic compounds showed a 20% increase in the gastric phase. Persea americana Mill. seed ingredient (3.08 μg/mL) showed total in vitro inhibition of clinical and reference strains of H. pylori, likewise, the lipophilic fraction had a lower inhibition concentration (2.59 μg/mL) regardless of the strains. Among the mechanisms found in silico, inhibition of target proteins such as CagA, BabA, and MUC5 were observed, as virulence factors involving adherence and bacterial pathogenicity. This research provides evidence that food ingredient from P. americana seed has antimicrobial in vitro potential against H. pylori clinical strains, through phenolic and mainly lipophilic compounds, opening new scientific evidence that supports the P. americana seed's traditional use.

Extranodal, nasal, natural Killer T-cell lymphoma of the lacrimal gland: A case report

Natural killer T-cell lymphomas involving the lacrimal gland are extremely rare. The prognosis of this type of lymphoma is poor, with 12-month mortality rates over 87%. In this case report, we present a patient with an isolated compromise of the right lacrimal gland by an extranodal, nasal, natural killer T-cell lymphoma treated with stereotactic radiotherapy with a free event follow-up of 12 years, an uncommonly long survival.

Abstract 3820: Impact of primary site in early-stage follicular lymphoma on patient outcomes: Analysis of a large national database

Abstract Introduction: Follicular lymphoma (FL) is the most common indolent Non-Hodgkin lymphoma and is associated with better outcomes compared to other types of lymphoma. Despite this, cure is usually elusive and most patients experience multiple relapses within their lifetime. Previous studies have identified risk factors associated with worse outcomes, but little is known about the role of primary disease site in FL. We sought to investigate the outcomes of patients with extranodal early-stage FL compared to nodal disease using a large national cancer database. Methods: The Surveillance, Epidemiology, and End Results (SEER) public database was used to identify and extract data for patients with FL. Early-stage disease was defined as stage I or II by the Ann Arbor staging system. Most patients in the database were diagnosed after 2000 so this was used as the diagnosis year cutoff and also to reflect the impact of recent management strategies on outcomes. Patients were divided into two groups based on their primary disease site. These two groups were nodal (includes spleen) and extranodal. Treatment effect (surgery, radiation, or chemotherapy) was analyzed when available. Survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional hazards models were used for adjusted survival analyses. Results: A total of 13,400 patients with FL of all histologic grades diagnosed between 2000 and 2015 were identified in the SEER database. The median age at diagnosis was 65 years (2-100). A majority of patients were Caucasian (81%), had stage I disease (62%), and belonged to the nodal FL group (79%). Median overall survival (OS) for patients with nodal FL was 181 months [95% CI (175-187)]. Median OS for extranodal FL was 189 months [95% CI (179-195)]. Extranodal FL was associated with better OS compared to the nodal group [HR=0.89, 95% CI (0.84-0.96); p-value =0.00012] even after adjusting for age and race [HR=0.84, 95% CI (0.79-0.90); p-value &amp;lt;0.0001]. Conclusions: In this analysis of a large national cancer database, early-stage FL presenting as extranodal disease can be seen in about 20% of patients and is associated with slightly better outcomes. Citation Format: Olivia Davis, Rana Kasht, Andrew Cohoon, Silas Day, Sami Ibrahimi, Adam Asch, Taha Al-Juhaishi. Impact of primary site in early-stage follicular lymphoma on patient outcomes: Analysis of a large national database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3820.

Abstract 2997: Identification of novel long non-coding RNAs in mantle cell lymphoma patients

Abstract Mantle Cell Lymphoma (MCL) is a rare and incurable type of B-cell non-Hodgkin lymphoma that affects about 4,000 people per year in the United States. Despite intense research to identify novel therapeutic approaches, the median progression-free survival after first-line treatment is four years. For this reason, the discovery of novel therapeutic targets remains crucial. Over half of the human genome is actively transcribed as non-coding RNAs. Among them, the non-coding RNAs that are longer than 200 nucleotides are named long non-coding RNAs (lncRNAs). lncRNAs have been shown to play essential roles in several human diseases, including cancer, by modulating cell cycle, immune response, or stemness through their interactions with DNA, protein, and RNA. For this reason, we decided to perform an RNA sequencing (RNA-Seq) profiling to identify the dysregulated lncRNAs in MCL. In more detail, we performed RNA-Seq in a cohort of 18 MCL patients compared to normal B-cells from the peripheral blood of healthy donors (HD). Reads were first trimmed for quality filtering, and adapters were removed using Trim Galore. Trimmed reads were mapped to the human genome (HG38 assembly) using HISAT 2. All the reads mapped inside the genomic coordinates of lncRNAs, reported in the GTF annotation file of GENCODE v43, were counted by featureCounts. Differential expression analysis between MCL samples vs HD was performed by LIMMA. To validate the results obtained from our internal MCL cohort, we also downloaded publicly available RNA-Seq data of 16 MCL patients and analyzed them using the previously described pipeline. Our analyses revealed several dysregulations in lncRNA expression occurring in MCL. Precisely, we identified 385 upregulated and 387 downregulated lncRNAs (|log2FC| &amp;gt; 0.58 and adjusted p-value &amp;lt; 0.05) in our internal MCL cohort, and 63% of them were also confirmed in the external cohort. Notably, the lncRNA called MALAT1 showed the highest significant upregulation in both cohorts, reinforcing this lncRNA's pivotal role in cancer development. To study the potential involvement of MALAT1 in MCL, we compared the MCL samples with higher MALAT1 expression (upper quartile) against those with lower expression (lower quartile) in both cohorts. The identified differentially expressed genes were used as input for a mechanistic network-based topological pathway analysis using MITHrIL. The analysis revealed that the KEGG pathway "Cell Cycle" was among the top upregulated pathways in MCL samples with high MALAT1 expression, suggesting the relevance of this lncRNA in promoting cellular proliferation, as also reported in the literature for other tumor types. In conclusion, our is the first study to describe the novel dysregulation signature of lncRNAs in MCL in two independent cohorts. Citation Format: Alessandro LaFerlita, Satishkumar Singh, Anuvrat Sircar, Robert Baiocchi, Natarajan Muthusamy, Lapo Alinari, Narendranath Epperla, Lalit Sehgal. Identification of novel long non-coding RNAs in mantle cell lymphoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2997.

Abstract 7276: Potent anti-proliferative activity of brincidofovir in Diffuse Large B-cell Lymphoma with overexpression of transcriptional repressor TLE1

Abstract Introduction: Brincidofovir (BCV) is a biologically-active acyclic nucleoside phosphonate and clinically-approved anti-viral agent. Recently, BCV has been demonstrated to display potent anti-proliferative and immunogenic properties in NK/T cell lymphoma (NKTCL). However, its effect on other lymphoma types remain unclear. Methods: We investigated BCV in an expanded cohort of B-cell lymphoma cell-lines (diffuse large B-cell lymphoma [DLBCL], n = 16; Burkitt lymphoma, n = 2; Hodgkin lymphoma, n = 1), in comparison with NKTCL cell lines (n = 11). Mouse xenograft models were deployed to assess in vivo effects. Whole transcriptomic sequencing (RNAseq) was performed to examine Epstein-Barr virus (EBV) status and explore potential mechanisms of action. Results: BCV inhibited viability in all B-cell lymphoma cell-lines in a dose-dependent manner (IC50 0.0798 to 8.414 µg/ml). Marked sensitivity (IC50 &amp;lt; 1 µg/ml) was demonstrated in nine cell-lines, including the MYC/BCL2-rearranged double-hit DLBCL cell-line OCI-LY18 (IC50 0.5 µg/ml). Intraperitoneal BCV (40 mg/kg, 2X per week) inhibited tumor growth in NOD/SCID mice OCI-LY18 xenografts, compared with vehicle alone (p &amp;lt; 0.001, two-tailed t-test). RNAseq showed that most cell-lines (n = 16) were EBV negative. Interestingly, the transcriptional repressor TLE1 was amongst the top upregulated genes in the BCV-sensitive cell-lines (log2foldchange = 8.12, adjusted p = 0.0004). DLBCL patient samples from two independent datasets showed that TLE1-high tumors conferred worse overall survival (GSE11318, n = 200: HR 2.77, 95%CI 1.78 to 4.30, p &amp;lt; 0.0001; GSE10846, n = 414: HR 1.94, 95%CI 1.35 to 2.80, p = 0.0004). Gene set enrichment analysis showed that pathways involved in oxidative phosphorylation and oncogenic signaling were significantly upregulated in the BCV-resistant cell-lines compared to the rest. Notably, these findings are in stark contrast to NKTCL, in which TLE1 loss instead confers BCV sensitivity in vitro and is associated with poor survival outcomes in patients (n = 36; HR 3.44, 95% CI 1.23-10.49, p = 0.0301). Conclusions: Taken together, these results suggest that BCV may be a potential novel therapeutic agent for the treatment of B-cell lymphomas. Further work will be required to investigate the role of TLE1 and other molecular features as potential predictive biomarkers. Citation Format: Jing Yi Lee, Tun Kiat Ko, Elizabeth Chun Yong Lee, Bavani Kannan, Boon Yee Lim, Zhimei Li, Zexi Guo, Jui Wan Loh, Cedric Chuan-Young Ng, Kelila Xin Ye Chai, Nur Ayuni Binte Muhammad Taib, Kerry Lim, Dachuan Huang, Jing Quan Lim, Masatoshi Hazama, Koji Fukushima, Bin Tean Teh, Soon Thye Lim, Choon Kiat Ong, Jason Yongsheng Chan. Potent anti-proliferative activity of brincidofovir in Diffuse Large B-cell Lymphoma with overexpression of transcriptional repressor TLE1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7276.

Nodal Low-Grade B-Cell Lymphoma Co-Expressing CD5 and CD10 but Not CD23, IRTA1, or Cyclin D1: The Diagnostic Challenge of a Splenic Marginal Zone Lymphoma.

The diagnosis of lymphoma is based on histopathological and immunophenotypical features. CD5 and CD10 are traditionally considered a T-cell antigen and a germinal center B-cell antigen, respectively. It is very unusual for a low-grade B-cell lymphoma (BCL) to co-express CD5 and CD10. Although the biologic basis or clinical significance of such co-expression is unclear, this rare event may pose a significant diagnostic challenge. Here, we report a case of a 63-year-old male presenting with bilateral cervical lymphadenopathy and lymphocytosis. Histologically, the nodal tumor was largely diffuse with neoplastic small atypical lymphocytes co-expressing CD5, CD10, and CD20, but not CD23 or cyclin D1. The leukemic cells in the peripheral blood exhibited hairy projections. Taking together the marked splenomegaly, involvement of lymph nodes, bone marrow, and peripheral blood, a final diagnosis of splenic marginal zone lymphoma (SMZL) was reached. The patient was alive with partial response for 10 months after immunochemotherapy. The dual expression of CD5 and CD10 is extremely unusual for low-grade BCL and may lead to an erroneous diagnosis. Integrating the findings into peripheral blood smear tests, flow cytometry, histopathology, imaging, and clinical features is mandatory to exclude other lymphoma types and to reach a correct diagnosis, particularly for a case with nodal presentation.

Cutaneous lymphoproliferative disorders: Back to the future.

In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan-T-cell antigens and clonal T-cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T-cell proliferations, and monotypic immunoglobulin light-chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B-cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T-cell lymphoma (PCSM-TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T-cell or B-cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low-grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease-specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low-grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM-TCL as primary cutaneous CD4+ small/medium T-cell LPD and primary cutaneous acral CD8+ T-cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term "primary cutaneous marginal zone LPD," in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.

Insulin-like Growth Factor II mRNA-binding Protein 3 is a Highly Sensitive Marker for Intravascular Large B-cell Lymphoma: Immunohistochemical Analysis of 152 Pathology Specimens From 88 Patients.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non-germinal center B cells were detected in only 2 samples (P= 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.

Incidence trends for common subtypes of T-cell lymphoma in Taiwan and the United States from 2008-2020.

The incidence of T-cell lymphoma (TCL) has been continually increasing in Taiwan and the United States (US) in recent years. This epidemiological study using population-based registry data aimed to determine the incidence patterns of common subtypes of TCL in Taiwan from 2008-2020 and compare them with those in the US and the Asian/Pacific Islander (API) population. Subtypes included angioimmunoblastic T-cell lymphoma (AITL); extranodal NK/T-cell lymphoma, nasal or other type (ENKTL); peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); and anaplastic large cell lymphoma (ALCL). The total number of patients newly diagnosed with TCL during 2008-2020 was 4477, 3171, and 48,889 in Taiwan, API, and the US, respectively. Except the incidence rate of AITL in Taiwan, the incidence rates of these common TCL subtypes showed downward trends in all studied populations. There was also a significant increase in the relative frequency of AITL among TCL in Taiwan, with an annual percent change of 4.44 (p < 0.001), from 8.44% in 2002 to 20.63% in 2020. The rapid development of diagnostics may be the main factor contributing to this rise in incidence.

The Possible Role of Pathogens and Chronic Immune Stimulation in the Development of Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. The disease is very heterogeneous, with distinct genetic alterations in subtypes. The WHO 2022 5th edition classification identifies several minor groups of large B-cell lymphoma where the pathogenetic role of viruses (like EBV and HHV-8) is identified. Still, most cases fall into the group of DLBCL not otherwise specified (NOS). No review focuses only on this specific lymphoma type in the literature. The pathogenesis of this entity is still not fully understood, but several viruses and bacteria may have a role in the development of the disease. The authors review critical pathogenetic events in the development of DLBCL (NOS) and summarize the data available on several pathogenetic viruses and bacteria that have a proven or may have a potential role in the development of this lymphoma type. The possible role of B-cell receptor signaling in the microenvironment is also discussed. The causative role of the Epstein-Barr virus (EBV), human herpesvirus-8 (HHV-8), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and other viruses are explored. Bacterial infections, such as Helicobacter pylori, Campylobacter jejuni, Chlamydia psittaci, Borrelia burgdorferi, and other bacteria, are also reviewed.

Role and progress of allogeneic hematopoietic stem cell transplantation in the treatment of refractory/relapsed diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non Hodgkin's lymphoma. The current treatment plan can significantly improve the prognosis of patients, but about 30%-40% of DLBCL patients still experience drug resistance and relapse after treatment. For patients with refractory/relapse DLBCL, clinical treatment remains difficult and their prognosis is poor. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the most important curative methods for refractory/relapse DLBCL patients. This article will review the role and progress of allo-HSCT in the treatment of refractory/relapse DLBCL.

Comparison of chemotherapy outcomes between normal and high serum cortisol concentration in dogs with lymphoma.

Increased serum cortisol (COR) concentrations may induce glucocorticoid resistance by down-regulation of glucocorticoid receptor (GCR), resulting in decreased chemotherapy efficacy in dogs with lymphoma. Investigate the relationship between serum COR concentrations and chemotherapy outcomes in dogs with lymphoma. Thirty client-owned dogs with lymphoma, with serum COR concentration measured using serum samples collected at diagnosis. Retrospective study. Dogs were divided into 2 groups based on serum COR concentrations: a normal group (n = 16) with COR concentrations <6 μg/dL and a high group (14) with COR concentrations ≥6 μg/dL. We compared signalment, clinical signs, stage, type of lymphoma, adrenal gland size, alkaline phosphatase (ALP) activity, response to chemotherapy, progression-free survival (PFS), overall survival (OS), and rate of P-glycoprotein (P-gp)- and GCR-positive cells between the 2 groups. No significant differences were found in the demographic characteristics between the 2 groups. However, the high COR group exhibited a significantly lower response to chemotherapy, PFS, and OS compared with the normal COR group. Serum ALP activity was significantly higher in the high COR group than in the normal COR group. Adrenal gland size was also significantly larger in the high COR group. Although no significant differences were found in the rate of P-gp-positive cells between the 2 groups, the rate of GCR-positive cells was significantly lower in the high COR group. Our data suggests that measurement of serum COR concentrations may serve as a potential prognostic factor and evaluation index.