Cases Of Diffuse Large B-cell Lymphoma Research Articles

Factors determining whether diffuse large B-cell lymphoma samples are detected by flow cytometry.

Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. Cases with a final diagnosis of DLBCL that were analysed by eight-colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B-cell (GCB) and non-GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine-needle aspirates, or between samples from nodal compared to extranodal tissue. The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight-colour analysis, FCM fails to detect numerous cases of DLBCL.

Pseudotemporal ordering of spatial lymphoid tissue microenvironment profiles trails Unclassified DLBCL at the periphery of the follicle.

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas.

BCL6 Protein Expression Identifies Cases without BCL6 Gene Rearrangement in Non-Germinal Centre Diffuse Large B- Cell Lymphoma Cases

BCL6 gene rearrangements are the most frequent cytogenetic abnormality in Diffuse Large B-Cell Lymphoma (DLBCL), occurring in up to 64% of cases, suggesting a poorer prognosis and response to therapy. The aim of this study was to calculate the accuracy and predictive power of BCL6 IHC in identifying BCL6 gene rearrangements. A search for DLBCL cases was performed on the laboratory information system. We retrospectively analysed 46 cases of DLBCL, and correlated BCL6 protein expression with gene rearrangement status. Of the 46 cases, 39 (84.78%) showed positive BCL6 protein expression by IHC. In comparison, only 10 (21.74 %) samples presented with gene rearrangements. There were 8 cases positive for BCL6 IHC with gene translocations and 5 cases were negative for both protein expression and gene rearrangements. BCL6 IHC had a sensitivity of 80% and a specificity of 14%. Furthermore, the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were 21% and 71%, respectively. BCL6 rearrangement was more common in cases with a Non-Germinal Centre (GC) Cell of Origin (COO) (45.5%) as compared to the GC group (14.3%). When stratifying the analysis according to the COO, the sensitivity and NPV of BCL6 IHC in the non-GC group were both 100%, while the same parameters were considerably poorer in the GC cases. BCL6 protein expression did not correlate with the presence of BCL6 gene rearrangements in HIV related DLBCL cases. However, lack of BCL6 protein expression may be used to identify cases without a BCL6 gene rearrangement, particularly in non-GC COO.

A rare testicular diffuse large B-cell lymphoma case with neurological initial presentation.

A rare testicular diffuse large B-cell lymphoma case with neurological initial presentation.

Development of a radiomic-clinical nomogram for prediction of survival in patients with diffuse large B-cell lymphoma treated with chimeric antigen receptor T cells.

In our current work, an 18F-FDG PET/CT radiomics-based model was developed to assess the progression-free survival (PFS) and overall survival (OS) of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received chimeric antigen receptor (CAR)-T cell therapy. A total of 61 DLBCL cases receiving 18F-FDG PET/CT before CAR-T cell infusion were included in the current analysis, and these patients were randomly assigned to a training cohort (n = 42) and a validation cohort (n = 19). Radiomic features from PET and CT images were obtained using LIFEx software, and radiomics signatures (R-signatures) were then constructed by choosing the optimal parameters according to their PFS and OS. Subsequently, the radiomics model and clinical model were constructed and validated. The radiomics model that integrated R-signatures and clinical risk factors showed superior prognostic performance compared with the clinical models in terms of both PFS (C-index: 0.710 vs. 0.716; AUC: 0.776 vs. 0.712) and OS (C-index: 0.780 vs. 0.762; AUC: 0.828 vs. 0.728). For validation, the C-index of the two approaches was 0.640 vs. 0.619 and 0.676 vs. 0.699 for predicting PFS and OS, respectively. Moreover, the AUC was 0.886 vs. 0.635 and 0.778 vs. 0.705, respectively. The calibration curves indicated good agreement, and the decision curve analysis suggested that the net benefit of radiomics models was higher than that of clinical models. PET/CT-derived R-signature could be a potential prognostic biomarker for R/R DLBCL patients undergoing CAR-T cell therapy. Moreover, the risk stratification could be further enhanced when the PET/CT-derived R-signature was combined with clinical factors.

Time-Related Vascular Inflammatory Response to COVID-19 Assessed by 18F-FDG PET/CT in Follow-Up Tumor Patients.

This study aimed to assess COVID-19's effects on vascular inflammatory response, by evaluating 18-Fluorodeoxyglucose (18F-FDG) uptake via positron emission tomography/computed tomography (PET/CT) in the artery of diffuse large B cell lymphoma (DLBCL) patients before and after infection with COVID-19. Thirty-five DLBCL patients administered the chemotherapy regimen R-CHOP and examined by oncological 18F-FDG PET/CT imaging twice from August 2022 to February 2023 for pre-treatment evaluation or assessment of treatment efficacy were enrolled. Seventeen patients were confirmed with COVID-19 within the study period. Arterial wall FDG uptake was semi-quantitatively analyzed as TBR (target-to-blood pool ratio) in 14 different vascular regions using oncological 18F-FDG PET/CT. Based on COVID-19 course and the two PET/CT scans, we further analyzed time-related FDG uptake for vascular walls in DLBCL patients with COVID-19. Arterial TBRs were higher in the last PET/CT examination than previous ones in all patients with or without COVID-19. Besides the ascending aorta, ΔTBR (last PET/CT scanning's TBR minus previous PET/CT scanning's TBR) were not significantly different between the COVID-19 and Control groups. However, cases scanned ≤30 days from infection had remarkably higher ΔTBRs in comparison with those assessed >30 days post-infection in the COVID-19 group (p<0.05). A moderate inverse correlation was observed between ∆Global TBR (last PET/CT scanning's average TBR value minus previous PET/CT scanning's average TBR value) and time distance from COVID-19 onset to 18F-FDG PET/CT scan (Spearman's rho=-0.591, P=0.012). Interestingly, there were no differences of changes of TBR between different purpose of PET/CT examination group. This work firstly suggested vascular inflammation is elevated in the early post-COVID-19 phase in DLBCL cases compared with prolonged post-COVID-19 phase or controls. Increasing attention should be paid to these patients and the protection of their vascular function and complications in early COVID-19.

Polyamine catabolism is concentrated in tumor-associated histiocytes in diffuse large B-cell lymphoma and classic Hodgkin lymphoma

Polyamines are cationic molecules necessary for cell survival, growth, and replication [1–5]. Polyamines come in a variety of structural forms and are principally regulated by two enzymes, spermine/spermidine acetyltransferase-1 (SAT1) and ornithine decarboxylase-1 (ODC1). SAT1 targets the polyamines spermidine and spermine for degradation via acetylation, while ODC1 is involved in converting the polyamine precursor molecule to more complex polyamines [6–8]. Polyamines and their regulatory enzymes have been implicated in tumor metastasis [9,10] and in crosstalk between oncogenes [11–13] in numerous types of cancer, but their role has never been evaluated in B-cell malignancies. In this study, we examine the expression of SAT1 in diffuse large B-cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). We found that SAT1 is expressed in all examined cases of DLBCL (n = 15) and HL (n = 5), though the levels of expression across cases vary. We also note that SAT1 expression appears to be concentrated in tumor-associated histiocytes, rather than tumor cells in both DLBCL and HL. We propose that these findings indicate that the polyamine catabolic enzyme, SAT1, plays an unappreciated role in the pathogenesis of B-cell neoplasms.

Presence of EBV antigens detected by a sensitive method in pediatric and adult Diffuse Large B-cell lymphomas.

In 2017, the World Health Organization (WHO) confirmed a new entity, Epstein Barr virus (EBV) + Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS). Traces of EBV transcripts were described in lymphomas, including DLBCL, that were diagnosed as EBV negative by conventional methods. The aim of this study was to detect viral genome by qPCR, as well as LMP1 and EBNA2 transcripts, with a more sensitive method in DLBCL cases from Argentina. Fourteen cases originally considered as EBV negative expressed LMP1 and/or EBNA2 transcripts. In addition, LMP1 and/or EBNA2 transcripts were also observed in bystander cells. However, EBERs+ cells cases by conventional ISH showed higher numbers of cells with LMP1 transcripts and LMP1 protein. In the cases that were EBERS- in tumor cells but with expression of LMP1 and/or EBNA2 transcripts, the viral load was below the limit of detection. This study provides further evidence that EBV could be detected in tumor cells by more sensitive methods. However, higher expression of the most important oncogenic protein, LMP1, as well as increased viral load, are only observed in cases with EBERs+ cells by conventional ISH, suggesting that traces of EBV might not display a key role in DLBCL pathogenesis.

Pancreatic Diffuse Large B-cell Lymphoma in the US Population.

Pancreatic lymphomas (PLs) represent <2% of all lymphomas and <0.5% of all pancreatic neoplasms. An accurate histologic diagnosis of PL is needed to predict prognosis and adequately treat the patient. This study aims to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of pancreatic diffuse large B-cell lymphoma (DLBCL). Demographic and clinical data from 493 cases of DLBCL of the pancreas were identified between 2000 and 2018 using the Surveillance, Epidemiology, and End Results (SEER) database. The most common age group was between the ages of 70 and 79 years (27.0%).While 44%of cases involved distant sites (a proxy for secondary pancreatic DLBCL), regional and localized involvement was seen in 33%, with the most common cause of death being a primary pancreatic DLBCL. Most patients (71%) received only chemotherapy (systemic therapy). The overall five-year observed survival was 46% (95% CI, 43.5-48.3). The one-year and five-year survival with chemotherapy only was 68% (95% CI, 65.3-70.3) and 48% (95% CI, 44.7-50.5), respectively. The one-year and five-year survival with surgery and chemotherapy was 96% (95% CI, 91.3-99.9) and 80% (95% CI, 71.4-89.2), respectively. Surgery with chemotherapy (HR: 0.397 (95% CI, 0.197-0.803), p = 0.010) were both positive predictors in survival prognosis. Multivariable analysis identified age >55 years (HR: 2.475 (95% CI, 1.770-3.461), p < 0.001), distant stage (HR: 6.894 (95% CI, 4.121-11.535), p < 0.001), and undergoing no surgery (HR: 2.610 (95% CI, 1.307-5.215), p = 0.007) as negative predictors for survival. PLs are rare malignant pancreatic neoplasms with DLBCL being the most common histological subtype. An accurate and timely diagnosis of pancreatic DLBCL is necessary to implement effective treatments and reduce mortality. Systemic therapy (chemotherapy) with or without surgical therapy improved survival. Increased age and regional and distant spread negatively impacted survival.

BTG2 SUPER‐ENHANCER MUTATIONS DISRUPT TFAP4 BINDING AND DYSREGULATE BTG2 EXPRESSION IN DIFFUSE LARGE B‐CELL LYMPHOMA

Introduction: Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy, remains incurable in ∼40% of patients. Coding-genome sequencing efforts identified several genes/pathways altered in this disease, as well as genetic subgroups of potential clinical relevance. However, the large non-coding portion of the genome remained largely unexplored. We recently identified a pervasive hypermutation mechanism targeting active super-enhancers (SEs) in >90% of DLBCL and leading to dysregulation of multiple genes, including well-known lymphoma oncogenes (Bal et al., Nature 2022). As evidence of oncogenic relevance, we demonstrated that mutational hotspots in the BCL6, BCL2 and CXCR4 SEs impair the binding of specific transcriptional repressors, preventing the gene negative regulation and creating oncogenic dependencies in DLBCL cells. Here we aimed to define the pathogenic role of mutations targeting the intragenic SE (iSE) of the BTG2 gene, the second most commonly mutated in DLBCL. BTG2 encodes a member of the B-cell translocation gene (BTG)/TOB family involved in transcriptional co-activation and modulation of mRNA abundance. BTG2 is also a recurrent target of somatic missense mutations (6%–11% of DLBCL), suggesting a major role in the pathogenesis of this disease. Methods: We screened 243 DLBCL cases for the presence of mutational hotspots within the BTG2-iSE, and combined in silico prediction, DNA-binding assays (Reverse-ChIP, electromobility-shift assay, ChIP-qPCR), RNA-seq and CRISPR/Cas9 editing approaches in isogenic BTG2 mutant versus WT DLBCL cell lines to identify transcription factors bound to the SE and disrupted by the mutation. Results: We identified a recurrent mutational cluster affecting the BTG2-iSE in 52/243 (21%) DLBCLs, with preferential enrichment in ST2 subgroup. CRISPR-Cas9 mediated correction of the mutation in 3 DLBCL cell lines led to counter selection and reduced BTG2 expression, consistent with oncogenic addiction. In silico motif prediction and in vitro DNA-binding assays, followed by validation in multiple isogenic DLBCL cell lines, identified TFAP4 as a major transcription factor that binds to the WT, but not to the mutated site. TFAP4 is an important regulator of B-cell proliferation and cell fate decisions, which can function as a transcriptional activator or repressor in germinal center B-cells, and acts downstream of/in parallel with c-MYC. Of note, introduction of SE hotspot mutations in WT DLBCL cells was associated with increased BTG2 expression, confirming a direct link between SE mutations and deregulated gene expression through escape from TFAP4-mediated suppression. Conclusions: These findings suggest a major role for BTG2 deregulation by SE aberrant somatic hypermutation in the pathogenesis and heterogeneity of DLBCL, with implications for precision classification and potential therapeutic targeting of DLBCL. Keywords: aggressive B-cell non-Hodgkin lymphoma, tumor biology and heterogeneity No conflicts of interests pertinent to the abstract.

APR‐246 TRIGGERS FERRITINOPHAGY AND FERROPTOSIS OF DIFFUSE LARGE B‐CELL LYMPHOMA CELLS WITH DISTINCT TP53 MUTATIONS

Purpose: Recently, seven diffuse large B-cell lymphoma (DLBCL) genotypes were defined, among which the A53 type showed adverse outcomes. Thus, it is necessary to explore promising anticancer drugs and therapies for TP53 dysfunction patients. APR-246 is a promising compound to combat mutant p53 in solid and hematological tumors, but the effect of APR-246 on DLBCL remains unclear. Methods: A set of 2464 DLBCL cases from multiple cohorts including our center, was integrated to identify the type and localization of TP53 mutations and clinical impacts. APR-246 was applied in TP53-mutated DLBCL cells and xenograft mouse models to explore the anti-tumor effect and the underlying mechanism. Results: Of all patients, 16% contained TP53 mutations. TP53 mutations correlated with poor overall survival (OS) and progression-free survival (PFS) in all cases. Notably, TP53single mutations in the DBD (exons 5-8) resulted in poor OS and PFS, but those on the exons (3-4, 9-11) outside the DBD. DLBCL cells carrying exons 5 and 7 or intact TP53 mutations showed more sensitivity to APR-246 than those containing spliced mutations or null TP53. DLBCL cells with knocked-out TP53 showed less sensitivity to APR-246. APR-246 also significantly inhibited the DLBCL tumor growth in xenograft animal model. The decreased cell viability induced by APR-246 was almost completely rescued by either the iron chelater deferoxamine (DFO) or ferrostatin-1 (Fer-1), indicating that ferroptosis mediates cell death. APR-246-induced cell death is an action involving ROS production, which was not altered by knockout of TP53 in OCI-LY7. However, only ferroptosis was induced by APR-246 in OCI-LY3, TMD8 and TP53-knockout OCI-LY7 cells, indicating that APR-246-induced autophagy in OCI-LY7 was TP53-dependent. Further, the cells re-expressing wild-type p53 showed the similar response as OCI-LY3 harboring wild-type p53 to APR-246, while the cells with re-expressed p53 mutant showed the similar response as OCI-LY7 to APR-246. The expression of ALOX5, ALOX12, and ALOX15 were increased in DLBCL cells after APR-246 treatment for 24 h. The LC3-II level was enhanced while the autophagy substrate SQSTM1 was reduced by APR-246 treatment, confirming APR-246 induces autophagy in OCI-LY7 cells. Additionally, FTH1, NCOA4 and HERC2 were also examined in TP53 knockout DLBCL cells, and the data demonstrated that APR-246 had no effect on the level of these proteins, indicating that APR-246 restored p53 was involved in ferritinophagy in OCI-LY7 cells. These findings were further confirmed in OCI-LY7 TP53-KO cells with re-expressing mutant or wild-type p53. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers, Genomics, Epigenomics, and Other -Omics No conflicts of interests pertinent to the abstract.

A case of lymphoma mimicking infected internal iliac artery aneurysm

BackgroundMalignant lymphoma rarely mimics an infected arterial aneurysm and a ruptured arterial aneurysm because of similar imaging findings, leading to misdiagnosis. The hematomas of ruptured aneurysms are radiologically difficult to distinguish from those of malignant lymphoma in emergency settings. Hence, a definitive diagnosis is crucial to avoid unnecessary surgery.Case presentationA man in his 80s with hematuria and shock vital had right internal iliac artery aneurysm (IIAA) and perianeurysmal fluid retention, which appeared to be a ruptured or an infected aneurysm. Treatment was initiated for infected IIAA instead of for ruptured IIAA. Systemic inflammatory response syndrome developed, and the infectious sources were assessed. Pacemaker lead and urinary tract infections were identified and treated; however, blood pressure was unstable. The aneurysm was treated with endovascular aortic aneurysm repair following antibiotic therapy; however, fluid retention increased, and inflammatory status and hematuria deteriorated. Open surgical conversion was performed to manage the infected lesions. Although an iliopsoas abscess was detected during surgery and nephrectomy and ureterectomy were performed to control the hematuria, analysis of the removed tissues led to the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL).ConclusionsWe encountered a case of DLBCL with imaging findings mimicking an infected internal iliac artery aneurysm, and definitive diagnosis was made more than 2 months after the initial examination. Definitively diagnosing malignant lymphoma around an iliac artery aneurysm based merely on symptoms and imaging findings is extremely difficult. Thus, histological examination should be actively performed in atypical infected aneurysms.

The Prognostic Impact of Tumor Microenvironment and Checkpoint Blockade-Associated Molecules (PD-1, PD-L1, CD163 and CD14) in Nodal Diffuse Large B-cell Lymphoma, NOS.

It is aimed to determine expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), CD163 and CD14 in diffuse large B-cell lymphomas (DLBCL), and whether these markers may predict prognosis in DLBCL cases. A total of 52 nodal DLBCL, NOS cases with no known extranodal involvement at the time of diagnosis were evaluated. PD-1, PD-L1, CD163, and CD14 were studied by immunohistochemistry. The relationships between the results and clinical and laboratory prognostic markers were investigated. It was observed that patients with PD-1 expression < 5 positive cells/HPF had worse overall survival. No significant relationship was found between survival and PD-L1, CD163 and CD14 expressions. In addition, cases that are > 60years of age, that have Eastern Cooperative Oncology Group (ECOG) performance score ≥ 2, stage IV disease, high International Prognostic Index score score (≥ 3), elevation of LDH, low albumin level, low hemoglobin level, low peripheral blood lymphocyte count, high peripheral blood neutrophil/lymphocyte ratio, high peripheral blood platelet/lymphocyte ratio were found to have worse overall survival. It was concluded that in patients with low number of PD-1 positive tumor-infiltrating lymphocytes have low survival rates and therefore PD-1 expression may be useful in indicating prognosis.

Long-term efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma achieving a complete response with pixantrone.

The prognosis of diffuse large B-cell lymphoma (DLBCL) patients with refractory or multiply relapsed (R/R) disease is disappointing. Pixantrone is currently approved as third or fourth line regimen, with encouraging results, even if long-term follow-up data are limited. In this post-hoc analysis of our observational study, we retrospectively investigated disease outcome and clinical characteristics of 16 R/R DLBCL patients who achieved a complete response with pixantrone. Pixantrone was administered as third or fourth line in 12/16 (75%) and 4/16 (25%) cases. After a median follow-up of 24 months, 14/16 patients (87.5%) were alive (causes of death were progressive disease and secondary acute myeloid leukemia, one case each). Median progression-free survival was 23.8 months, median duration of response was 17.8 months and median overall survival (OS) was not reached (2-years OS was 84%). A significant proportion of patients achieved a long-lasting response >12 months (7/16 cases). Response to prior therapy did not influence long-term remission after pixantrone. In this real-life experience, pixantrone demonstrated long-term efficacy in a cohort of R/R DLBCL cases who had previously received at least two prior regimens; many of whom had characteristics associated with poor prognosis.

A Decision-tree Approach to Stratify DLBCL Risk Based on Stromal and Immune Microenvironment Determinants.

A Decision-tree Approach to Stratify DLBCL Risk Based on Stromal and Immune Microenvironment Determinants.

Real-world data for lenalidomide maintenance in responding patients of diffuse large B-cell lymphoma.

Approximately 40% patients of diffuse large B-cell lymphoma (DLBCL) would develop disease recurrence/progression after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single-drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti-tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long-term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R-CHOP treatment. This retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6-8cycles of R-CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n=141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide, n=50) and drug-free maintenance treatment (control, n=91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression-free survival (PFS) was taken as the primary outcome. Of the total 141 subjects, the median follow-up time was 30.9months (range, 5.7-68.9months). The 2-year PFS was 84% (95% CI: 74%-94%) in the lenalidomide group and 53% (95% CI: 43%-63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9months (HR=0.32; 95% CI: 0.16-0.63; p=0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR=0.42; 95% CI: 0.16-1.12; p=0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1-2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3-4 adverse reaction. Two-year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first-line R-CHOP treatment.

Primary Bone Lymphoma: A Review of the Literature with Emphasis on Histopathology and Histogenesis.

Primary bone lymphoma (PBL) is a rare neoplasm of malignant lymphoid cells presenting with one or more bone lesions without nodal or other extranodal involvement. It accounts for approximately 1% of all lymphomas and 7% of malignant primary bone tumors. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) represents the predominant histological type and constitutes over 80% of all cases. PBL may occur at all ages with a typical diagnosis age of 45-60 years and a slight male predominance. Local bone pain, soft tissue edema, palpable mass and pathological fracture are the most common clinical features. Diagnosis of the disease, which is frequently delayed due to its non-specific clinical presentation, is based on the combination of clinical examination and imaging studies and confirmed by combined histopathological and immunohistochemical examination. PBL can develop in any part of the skeleton, although it occurs most commonly in the femur, humerus, tibia, spine and pelvis. The imaging appearance of PBL is highly variable and unspecific. In terms of the cell-of-origin, most cases of primary bone DLBCL (PB-DLBCL), NOS belong to the germinal center B-cell-like subtype and specifically originate from germinal center centrocytes. PB-DLBCL, NOS has been considered a distinct clinical entity based on its particular prognosis, histogenesis, gene expression and mutational profile and miRNA signature. PBL carries a favorable prognosis, especially when treated with combined chemoradiotherapy.

Clinicopathological analysis of primary thyroid non-Hodgkin lymphoma: a single-center study.

Primary thyroid lymphoma (PTL) is very rare. The aim of this study was to describe the clinical characteristics, pathological features, and survival outcomes of primary thyroid non-Hodgkin lymphoma, including the diagnostic value of clonal immunoglobulin (Ig) gene rearrangements in diagnosing mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland with co-existing Hashimoto thyroiditis (HT). Paraffin-embedded tissues of patients diagnosed in our institute with PTL between 2007 and 2021 were collected. Clinicopathological features and follow-up data were retrospectively analyzed. Analysis of clonal Ig gene rearrangements were performed in patients with suspected PTL. Of the 22 patients included in our study, 17 were female. The median age at diagnosis was 65.5 years (range, 44-80 years). We detected 11 cases of diffuse large B-cell lymphoma (DLBCL), 10 cases of MALT lymphoma, and 1 case of T-cell lymphoma. A total of 18 patients (81.8%) had early stage (I/II) disease. B-cell lymphoma showed diffuse positivity for CD20 but negative markers for thyroid-origin cells. Double-hit and triple-hit lymphomas were not found in the 8 DLBCL cases, and 2 cases of HT with lymphoid tissue dysplasia were diagnosed with MALT lymphoma with gene rearrangement testing. The median follow-up time was 47 months (range, 4-160 months), and the overall survival was 80% for MALT lymphoma (8 of 10), 72.7% for DLBCL lymphoma (8 of 11), and 100% for T-cell lymphoma (1 of 1). There was no significant difference between the groups. PTL mostly affects middle-aged and older adult females with HT, and its main histological type is non-Hodgkin B-cell lymphoma. For patients with HT along with a histologically benign lymphoepithelial lesion, the identification of clonal Ig gene rearrangements is important for differential diagnosis. The prognosis between DLBCL and MALT is not statistically significant.

Non-germinal center B-cell subtype of pediatric diffuse large B-cell lymphoma in Japan: A retrospective cohort study.

Diffuse large B-cell lymphoma (DLBCL) is classified into two molecular subtypes according to its cell of origin: germinal center B-cell (GCB) subtype and activated B-cell/non-GCB subtype. This latter subtype shows a poorer prognosis in adults. However, in pediatric DLBCL, the prognostic impact of the subtype is yet to be clarified. This study sought to compare the prognosis between GCB and non-GCB DLBCL in a large number of cases in children and adolescents. In addition, this study intended to describe the clinical, immunohistochemical, and cytogenetic characteristics of these two molecular subtypes of DLBCL, and consider differences in the biology, frequency, and prognosis of GCB and non-GCB subtypes in pediatric versus adult DLBCL or in Japanese versus Western pediatric DLBCL patients. We selected mature B-cell lymphoma/leukemia patients for whom specimens had been submitted to the central pathology review in Japan between June 2005 and November 2019. We referred the past studies on Asian adult patients and Western pediatric patients to compare with our results. Data were obtained from 199 DLBCL patients. The median age of all patients was 10years, with 125 patients (62.8%) in the GCB group and 49 (24.6%) in the non-GCB group other than 25 cases whose immunohistochemical data were insufficient. Overall, the percentage of translocation of MYC (1.4%) and BCL6 (6.3%) was lower than in adult and Western pediatric DLBCL cases. The non-GCB group showed a significantly higher proportion of females (44.9%), a higher incidence of stage III disease (38.8%), and B-cell lymphoma 2 (BCL2)-positivity in immunohistochemistry (79.6%) compared to the GCB group; however, no BCL2 rearrangement was observed in both GCB and non-GCB groups. The prognosis did not differ significantly between the GCB and non-GCB groups. This study including a large number of non-GCB patients showed the same prognosis between GCB and non-GCB groups and suggested a difference in the biology of pediatric and adolescent DLBCL compared to adult DLBCL as well as between Asian and Western DLBCL.

MUM-1 in canine lymphoma: A pilot study.

Expression of interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) in peripheral T-cell lymphoma (PTCL) in people is associated with a poorer survival outcome compared to cases of PTCL lacking MUM1 expression. The aim of this study was to determine whether MUM1 is expressed in canine peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). For comparison, the presence of MUM1 antigen was also investigated in canine diffuse large B cell lymphoma (DLBCL). Nine cases of PTCL-NOS and 9 cases of DLBCL diagnosed by a commercial veterinary diagnostic laboratory were selected. Positive immunohistochemical labeling for MUM1 was observed in PTCL-NOS (2 out of 9 cases) and DLBCL (3 out of 9 cases). These findings suggest that a subset of neoplastic T and B lymphocytes can express MUM1. The role of MUM1 in the biological behavior and outcome of canine lymphoma (CL) requires further investigation on a larger number of cases.