Primary Diffuse Large B-Cell Lymphoma of the Breast with MYC and BCL2 Rearrangements with Terminal Deoxynucleotidyl Transferase Expression: A Case Report.

Introduction: Primary breast lymphoma represents only 1% of non-Hodgkin lymphomas. The most common histology is diffuse large B-cell lymphoma. When dual translocations of MYC and BCL2 or BCL6 occur, it is referred to as "high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6" according to the 4th edition of the WHO classification of hematolymphoid tumors. The expression of tdt in this type of malignancy is exceptional. Case Report: This is a case of a 54-year-old woman presenting with a rapidly growing painless mass. Ultrasound-guided core biopsy of the breast mass showed infiltrate of medium-sized neoplastic lymphocytes which stained as CD79a-positive B cells co-expressing CD10, BCL2, tdt, and MYC. Ki-67 is positive in 80%. There was rearrangement of MYC and BCL2 at FISH. Positron emission tomography (PET) scan was negative elsewhere. Final diagnosis was a DLBCL of the breast with tdt expression. She was treated with 6 cycles of R-hyperCVAD/MA (R = rituximab, C = cyclophosphamide, V = vincristine, A = cytarabine, D = dexamethasone, M = methotrexate) and intrathecal chemotherapy (IT CT). Restaging PET shows resolution of all avid uptake. We did a review of literature showing the importance of giving an intensive chemotherapy regimen, high-dose methotrexate, cytarabine, and IT CT for central nervous system (CNS) prophylaxis. Conclusion: Primary DLBCL of the breast with rearrangement of MYC and BCL2 and tdt expression is an aggressive disease not very well studied that needs to be treated with an intensive CT and CNS prophylaxis. Stem cell transplant could be given after first remission.

Herpes Simplex Virus Necrotic Lymphadenitis Masquerading as Lymphoma.

In immunocompromised patients, the rapid development of lymphadenopathy could pose a few diagnostic challenges. This is important, especially with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) which can manifest with the development of infections or may even progress with transformation into a more aggressive form of the disease. We report a case of a patient with CLL/SLL who presented with fever and worsening dyspnea as well as inguinal lymphadenopathy upon evaluation. The excisional biopsy of affected lymph nodes revealed herpes simplex virus lymphadenitis confirmed by immunohistochemical staining. Flow cytometry showed no progression to diffuse large B-cell lymphoma. This case highlights the importance of considering a broad spectrum of differential diagnoses when assessing lymphadenopathy in immunocompromised patients receiving active immunosuppressive therapy.

Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

Diffuse large B-cell lymphoma in the uterus with unexpected manifestations: a case report.

BACKGROUND: Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract. CASE PRESENTATION: A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor). CONCLUSION: Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.

Cost-Effectiveness Analysis of Axicabtagene Ciloleucel vs. Standard of Care in Second-Line Treatment for Relapsed/Refractory Large B-Cell Lymphoma in Spain.

PURPOSE: To estimate the cost-effectiveness of axi-cel vs. salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem-cell transplantation (HDT+ASCT) for responders to second-line treatment for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). METHODS: A partitioned survival mixture-cure model comprising three health states was used to estimate the costs, life years gained (LYG), and quality-adjusted life years (QALYs) accumulated over a lifetime horizon. Overall survival, event-free survival, and time to the next treatment with axi-cel and HDT+ASCT were derived from the ZUMA-7 study. The total costs (EUR, 2022) included drug acquisition and administration, ASCT, subsequent treatment, disease and adverse event management, and palliative care. The unitary costs were derived from local databases and the literature. A 3% discount rate was applied to the costs and outcomes. RESULTS: Compared with HDT+ASCT, axi-cel provided higher LYG per patient (10.00 vs. 8.28 LYG/patient) and greater QALYs gained per patient (7.85 vs. 6.04 QALY/patient). The lifetime total costs were 343,581 EUR/patient with axi-cel vs. 257,994 EUR/patient with IQT+ASCT. The incremental cost-effectiveness ratio of axi-cel vs. HDT+ASCT was 49,627 EUR/LYG, and the incremental cost-utility ratio was 47,309 EUR/QALY. Sensitivity analyses confirmed the robustness of the model. CONCLUSION: Axi-cel is a potentially cost-effective alternative to HDT+ASCT for the treatment of R/R DLBCL in Spain.

CRISPR-Cas9 Knockout Screens Identify DNA Damage Response Pathways and BTK as Essential for Cisplatin Response in Diffuse Large B-Cell Lymphoma.

The recurrence of diffuse large B-cell lymphoma (DLBCL) has been observed in 40% of cases. The standard of care for refractory/relapsed DLBCL (RR-DLBCL) is platinum-based treatment prior to autologous stem cell transplantation; however, the prognosis for RR-DLBCL patients remains poor. Thus, to identify genes affecting the cisplatin response in DLBCL, cisplatin-based whole-genome CRISPR-Cas9 knockout screens were performed in this study. We discovered DNA damage response (DDR) pathways as enriched among identified sensitizing CRISPR-mediated gene knockouts. In line, the knockout of the nucleotide excision repair genes XPA and ERCC6 sensitized DLBCL cells to platinum drugs irrespective of proliferation rate, thus documenting DDR as essential for cisplatin sensitivity in DLBCL. Functional analysis revealed that the loss of XPA and ERCC6 increased DNA damage levels and altered cell cycle distribution. Interestingly, we also identified BTK, which is involved in B-cell receptor signaling, to affect cisplatin response. The knockout of BTK increased cisplatin sensitivity in DLBCL cells, and combinatory drug screens revealed a synergistic effect of the BTK inhibitor, ibrutinib, with platinum drugs at low concentrations. Applying local and external DLBCL cohorts, we addressed the clinical relevance of the genes identified in the CRISPR screens. BTK was among the most frequently mutated genes with a frequency of 3-5%, and XPA and ERCC6 were also mutated, albeit at lower frequencies. Furthermore, 27-54% of diagnostic DLBCL samples had mutations in pathways that can sensitize cells to cisplatin. In conclusion, this study shows that XPA and ERCC6, in addition to BTK, are essential for the response to platinum-based drugs in DLBCL.

Case Report: Post-transplant lymphoproliferative disorder as a serious complication of vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is an emerging field in transplant surgery. Despite overall positive outcomes, VCA confers risk for multiple complications related to the procedure and subsequent immunosuppression. Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoproliferative disorders occurring after solid organ and hematopoietic stem cell transplant. A patient with PTLD after bilateral upper extremity transplantation is presented as well as a review of all known cases of PTLD after VCA, with a focus on the unique epidemiology, presentation, and treatment in this population.

N-acetyltransferase 10 facilitates tumorigenesis of diffuse large B-cell lymphoma by regulating AMPK/mTOR signalling through N4-acetylcytidine modification of SLC30A9.

BACKGROUND: Accumulating studies suggested that posttranscriptional modifications exert a vital role in the tumorigenesis of diffuse large B-cell lymphoma (DLBCL). N4-acetylcytidine (ac4C) modification, catalyzed by the N-acetyltransferase 10 (NAT10), was a novel type of chemical modification that improves translation efficiency and mRNA stability. METHODS: GEO databases and clinical samples were used to explore the expression and clinical value of NAT10 in DLBCL. CRISPER/Cas9-mediated knockout of NAT10 was performed to determine the biological functions of NAT10 in DLBCL. RNA sequencing, acetylated RNA immunoprecipitation sequencing (acRIP-seq), LC-MS/MS, RNA immunoprecipitation (RIP)-qPCR and RNA stability assays were performed to explore the mechanism by which NAT10 contributed to DLBCL progression. RESULTS: Here, we demonstrated that NAT10-mediated ac4C modification regulated the occurrence and progression of DLBCL. Dysregulated N-acetyltransferases expression was found in DLBCL samples. High expression of NAT10 was associated with poor prognosis of DLBCL patients. Deletion of NAT10 expression inhibited cell proliferation and induced G0/G1 phase arrest. Furthermore, knockout of NAT10 increased the sensitivity of DLBCL cells to ibrutinib. AcRIP-seq identified solute carrier family 30 member 9 (SLC30A9) as a downstream target of NAT10 in DLBCL. NAT10 regulated the mRNA stability of SLC30A9 in an ac4C-dependent manner. Genetic silencing of SLC30A9 suppressed DLBCL cell growth via regulating the activation of AMP-activated protein kinase (AMPK) pathway. CONCLUSION: Collectively, these findings highlighted the essential role of ac4C RNA modification mediated by NAT10 in DLBCL, and provided insights into novel epigenetic-based therapeutic strategies.

Prognostic Significance of Bcl-2 Expression in Non-germinal Center B-cell-Like Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphomas (DLBCLs) are a group of malignant neoplasms with extensive clinical and molecular heterogeneity. Several key genetic aberrations have been identified, such as those involving the MYC, BCL6, and BCL2 genes. Prior studies on the prognostic significance of Bcl-2 protein expression in DLBCL have been contradictory, with some suggesting it has an adverse effect, while others have shown no such association. Bcl-2 is known to be more highly expressed in the non-germinal center B-cell-like (non-GCB) subtype compared to germinal center B-cell-like (GCB) DLBCL. Non-GCB status is associated with a less favorable prognosis. This study aimed to investigate whether the expression of Bcl-2 protein in non-GCB DLBCL influences response to treatment, progression-free survival, or overall survival. METHODS: In this retrospective study, we investigated whether there was a difference in the clinical outcomes of non-GCB DLBCL cases (n = 97) that were confirmed by immunochemistry to demonstrate high levels of Bcl-2 protein expression (>50% neoplastic cells stained) when compared to those who were deemed negative based on this criterion. Response to rituximab-based induction immunochemotherapy, five-year progression-free survival, and five-year overall survival were assessed. RESULTS: There was no statistically significant difference in response to treatment, five-year progression-free survival, or five-year overall survival between the patients who were positive for Bcl-2 (n = 70) compared to those who were considered Bcl-2 negative (n = 27). CONCLUSION: High levels of Bcl-2 protein expression do not appear to be of prognostic significance in non-GCB DLBCL and therefore Bcl-2 may not be a key therapeutic target in the treatment and improvement of clinical outcome in such cases.

ß-Sitosterol Inhibits Tumor Growth and Amplifies Rituximab Sensitivity through Acid Sphingomyelinase/Ceramide Signaling in Diffuse Large B-Cell Lymphoma.

Rituximab (RTX) resistance is a notable challenge in treating diffuse large B-cell lymphoma (DLBCL). ß-Sitosterol (ß-ST) is a plant sterol that has been found in a broad variety of fruits, spices, and medicinal plants. The antineoplastic properties of ß-ST are established in various solid malignancies; however, its effect on DLBCL is uncharted. This study investigates the role of ß-ST in DLBCL as well as the underlying mechanisms. Our findings indicated that ß-ST impeded DLBCL cell proliferation in a concentration- and time-dependent manner. ß-ST appeared to alter sphingolipid metabolism, facilitate acid sphingomyelinase (ASM) translocation to the plasma membrane, augment ceramide platforms through increased ceramide synthesis, and consequently induce apoptosis in DLBCL cells. Furthermore, we found that RTX initiated both apoptotic and survival pathways in vitro, with the former contingent on the transient activation of the ASM, and ß-ST could amplify the anti-DLBCL efficacy of RTX by modulating ASM/Ceramide (Cer) signaling. Collectively, our findings elucidate the mechanistic role of ß-ST in DLBCL and underscore its potential in amplifying the antineoplastic efficacy of RTX via ASM activation, proposing a potential avenue to improve the efficacy of RTX therapy.

Cuproptosis: Mechanism and Application in Lymphoma.

The cell death field has profited from the increasing attention of the scientific community and has been shown to lie at the very basis of cancer initiation and progression. Cuproptosis is a recently proposed method of cell death in 2022, and it is different from any previously reported method. The principle is that copper ions lead to aggregation and instability of intracellular proteins. An increasing number of researchers are dedicated to enriching the mechanism of cuproptosis and exploring its relationship with cancer. Studies have found that intracellular copper levels have an impact on the occurrence and development of lymphoma. The complexity of lymphoma and the limitations of treatment necessitate in-depth studies of the disease. We will review the mechanism of cuproptosis and its potential in lymphoma therapy.

Integrative analysis of cancer multimodality data identifying COPS5 as a novel biomarker of diffuse large B-cell lymphoma.

Preventing, diagnosing, and treating diseases requires accurate clinical biomarkers, which remains challenging. Recently, advanced computational approaches have accelerated the discovery of promising biomarkers from high-dimensional multimodal data. Although machine-learning methods have greatly contributed to the research fields, handling data sparseness, which is not unusual in research settings, is still an issue as it leads to limited interpretability and performance in the presence of missing information. Here, we propose a novel pipeline integrating joint non-negative matrix factorization (JNMF), identifying key features within sparse high-dimensional heterogeneous data, and a biological pathway analysis, interpreting the functionality of features by detecting activated signaling pathways. By applying our pipeline to large-scale public cancer datasets, we identified sets of genomic features relevant to specific cancer types as common pattern modules (CPMs) of JNMF. We further detected COPS5 as a potential upstream regulator of pathways associated with diffuse large B-cell lymphoma (DLBCL). COPS5 exhibited co-overexpression with MYC, TP53, and BCL2, known DLBCL marker genes, and its high expression was correlated with a lower survival probability of DLBCL patients. Using the CRISPR-Cas9 system, we confirmed the tumor growth effect of COPS5, which suggests it as a novel prognostic biomarker for DLBCL. Our results highlight that integrating multiple high-dimensional data and effectively decomposing them to interpretable dimensions unravels hidden biological importance, which enhances the discovery of clinical biomarkers.

Autologous stem cell transplant in fit patients with late relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy.

The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using the Kaplan-Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1-3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 years (range 19-78), and 36 (24%) patients were of ≥70 years. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70-78 years), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 vs 124.7 months, P=0.045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 vs 61.4 months, P <0.0001) and OS (17.8 vs 111.7 months, P=0.0004). There was no statistically significant difference in survival in patients who achieved PR vs CR, though numerically inferior in the former, with median PFS of 38.9 vs 59.3 months (P=0.23) and median OS of 78.3 vs 111.7 months (P=0.62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70-78 years at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.

Diffuse Large B-cell Lymphoma Complicated with Anti-3-hydroxy-3-methylglutaryl-Coenzyme A Reductase Immune-mediated Necrotizing Myopathy: A Case Report.

A 75-year-old woman presented with significant muscle weakness after statin use. A muscle biopsy revealed necrotizing myopathy, and the patient tested positive for serum anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, leading to a diagnosis of anti-HMGCR immune-mediated necrotizing myopathy (IMNM). Computed tomography revealed intraperitoneal lymphadenopathy, which was diagnosed as a diffuse large B-cell lymphoma. Immunostaining confirmed HMGCR expression in the lymphoma cells. The patient received chemotherapy and achieved complete remission of the lymphoma, along with nearly complete recovery from IMNM. Although the etiologies of IMNM and lymphoma remain unclear, HMGCR expression in lymphoma cells is likely to be associated with the development of IMNM.

Real-world evaluation of health-related quality of life in patients with diffuse large B-cell lymphoma based on a multinational survey.

Background: Real-world health-related quality of life (HRQoL) data in patients with diffuse large B-cell lymphoma (DLBCL) are scarce. This study is to compare patient-reported outcomes in patients with DLBCL across therapy lines and countries. Methods: Data were derived from the Adelphi DLBCL Disease Specific Programme™ from January 2021 to May 2021, a survey of physicians and their DLBCL patients in France, Germany, Italy, Spain, United Kingdom (UK), and the United States (US). Results: Overall, analysis was conducted on 441 patients with DLBCL across Europe and the US (mean age 64.6 years, 64% male); 68% had an Ann Arbor stage III and 69% had an Eastern Cooperative Oncology Group Performance Status of 0 to 1. The mean overall GHS/QoL was 54.1; patients on their 3L+ therapy had a lower mean GHS/QoL compared with patients on 1L/2L (P = 0.0033). Further to this, mean EQ-5D-5L utility score was reduced from 0.73 for patients on 1L therapy to 0.66 for patients on 3L+ therapies (P = 0.0149). Mean percentages of impairment while working and overall work impairment were lower for patients receiving 3L+ therapy (12.5% and 17.7%; respectively) than those on 1L therapy (35.6% and 33.8%; respectively). When comparing region, patients in the US had significantly better scores for all functioning and symptomatic scales (per EORTC QLQ-C30) and work impairment (per WPAI) vs. patients with DLBCL in Europe. WPAI scores indicate that the overall activity impairment in the US was 36.6% and in Europe ranged from 42.4% in the UK to 54.9% in Germany. Mean EQ-5D-5L utility score for the US was 0.80, compared to 0.60 - 0.80 across the countries in Europe. Regression analysis showed patients who relapsed after more than one year of treatment were associated with better patient reported outcomes than those who relapse after less than one year. Conclusion: Patient-reported outcomes of DLBCL patients remain poor and patients continue to experience considerable morbidity.

Primary diffuse large B-cell lymphoma of the lacrimal sac with involvement of maxillary sinus: a case report and review of literature.

Primary lacrimal sac lymphoma is a rare condition, often presenting with nasolacrimal duct obstruction. Herein, we present a unique case of diffuse large B-cell lymphoma (DLBCL) involving the lacrimal sac, maxillary sinus, and infraorbital nerve. Prompt diagnosis via biopsy is essential for timely treatment and the prevention of tumor progression. A 66-year-old female presented with intractable epiphora, infraorbital nerve hypesthesia, and medial canthal swelling. Imaging revealed a soft tissue mass in the right maxillary sinus extending into the right inferior orbit and nasal cavity. A biopsy confirmed DLBCL, prompting systemic chemotherapy. Residual disease prompted high-dose involved-site radiation, resulting in tumor regression. To our knowledge, this is the first case of primary DLBCL of the lacrimal sac with concurrent involvement of the maxillary sinus and infraorbital nerve. This case underscores the significance of lacrimal sac biopsy in refractory dacryocystitis or unilateral sinus disease and the effectiveness of multimodal treatment approaches in managing DLBCL.

HBx Integration in Diffuse Large B-cell Lymphoma Inhibits Caspase-3-PARP Related Apoptosis.

Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.

Clinicopathological differences in MYC and BCL2 protein expression between primary extranodal and nodal diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) exhibits clinical, genetic, and immunohistochemical heterogeneity. However, the differences between primary extranodal or nodal DLBCL and double-expressor lymphoma (DEL), which is characterized by high MYC and BCL2 expression, remain unclear. This study aimed to elucidate the clinicopathological features, response to therapy, and clinical outcomes of primary extranodal (n=61) and nodal (n=128) DLBCL. Patients with primary nodal DLBCL had higher BCL2 expression than those with extranodal DLBCL (p=0.048), with high MYC expression and DEL as poor prognostic factors. Conversely, in patients with primary extranodal DLBCL, high BCL2 expression, low BCL6 expression, non-germinal center B-cell-like type, and DEL indicated poor prognosis. DEL was significantly associated with progression free survival and overall survival in patients with primary extranodal DLBCL (p=0.014 and p=0.021, respectively) but not in patients with primary nodal DLBCL (p=0.37 and p=0.084, respectively). Our findings highlight primary extranodal DEL as a strong adverse prognostic factor in DLBCL.

Coexistence of large cell transformed mycosis fungoides and diffuse large B-cell lymphoma in one patient.

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma. The overall risk of developing DLBCL is increased in patients with other lymphomas, such as mycosis fungoides (MF). In this report, we present an 81-year-old female with early-stage MF who simultaneously progressed to tumor stage, large-cell transformed (LCT) MF and developed a primary DLBCL in a lymph node (LN). She presented with a tumor on her leg and new lymphadenopathy in her right axilla. Skin biopsy of the tumor revealed infiltration of large atypical CD3+, CD4+, and CD30+ cells, and a smaller portion of CD8+ cells in the dermis, consistent with LCT MF. Biopsy of the axillary LN revealed diffuse sheets of CD20+, BCL-2+, c-MYC+, and CD10- cells, highly suggestive of double expressor DLBCL. High-throughput sequencing revealed monoclonal T cells in the skin tumor and a monoclonal B-cell population in the LN. The above findings led to simultaneous diagnoses of LCT MF and nodal double expressor DLBCL. Our case demonstrates the importance of performing a full pathological workup in cutaneous T-cell lymphoma patients presenting with lymphadenopathy.