Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy composed of immature cells that exhibit plasmacytoid dendritic cell (pDC) differentiation. The diagnosis of BPDCN is often challenging due to its rarity and morphologic and phenotypic overlap with other hematologic malignancies, such as acute myeloid leukemia (AML). The emergence of tagraxofusp, a CD123-directed cytotoxin, and other novel therapies has underscored the importance of accurately diagnosing BPDCN. This review initially outlined the clinical and histopathological features of BPDCN, including patients with immunoblastoid morphology. Various proposed diagnostic criteria based on flow cytometry and immunohistochemistry findings were presented, highlighting critical points of caution in the diagnostic process. Strategies for detecting minimal residual disease or microinvasion in BPDCN, a significant clinical issue, were also discussed. Additionally, we reviewed the recurrent 8q24 (MYC) and MYB rearrangements observed in BPDCN, which can aid in diagnosis. Furthermore, we explored mature plasmacytoid dendritic cell proliferation (MPDCP) associated with myeloid neoplasm, which is characterized by a clonal proliferation of pDCs in cases with a defined myeloid neoplasm and may also serve as a potential differential diagnosis for BPDCN. Lastly, we discussed pDC-AML, characterized by pDC proliferation in AML cases, which can also be part of MPDCP and is often associated with frequent RUNX1 mutations. Overall, this review provides insights into BPDCN diagnosis and highlights the current challenges in its detection and differential diagnosis.

Little is known about real-world treatment practices for chronic lymphocytic leukemia (CLL) in Japan. We aimed to assess the time to discontinuation/dose reduction of Bruton tyrosine kinase inhibitors (BTKis) in patients with CLL in a real-world clinical setting in Japan. This was a retrospective observational database study using data from the Medical Data Vision database (from 1 May 2016 to 30 September 2021). Among the 483 patients with CLL who were treated with BTKis, 182 (37.7%) started treatment with a reduced dose of BTKi (lower than the standard dose), 302 (62.5%) experienced at least one dose reduction during the study period, and 123 (25.5%) discontinued BTKi treatment early (for any reason) during the study period. The median time to BTKi discontinuation was 52.3 weeks in 286 patients who started treatment with a standard dose and 57.1 weeks in 182 patients who started treatment with a reduced dose. The use of prophylaxis with anti-infectives was similar during treatment with BTKis and non-BTKis. There was no major difference in the incidence rate of cardiovascular-related adverse events during treatment with BTKis and non-BTKis. This study provides valuable information for future research on the treatment of CLL patients in Japan.

Primary central nervous system (CNS) lymphomas account for 1.9–3% of all brain tumors, with the majority being histologically classified as primary large B-cell lymphoma of the CNS (PCNS-LBCL). PCNS-LBCL is characterized by mature germinal center-exit B cells, and most cases of this phenotype are classified as activated B-cell-like phenotype according to gene expression profiling, or as non-germinal center B-cell-like phenotype (non-GCB type) according to Hans’s algorithm. Genetically, PCNS-LBCL often shows mutations in MYD88^L265P and CD79B^Y196, and is similar to MCD or C5 in genetic subtypes. Therefore, we here investigated the clinicopathological and molecular characteristics of primary CNS B-cell lymphomas (PCNSBLs), focusing on the differences in the frequency of MYD88^L265P and CD79B^Y196 mutations, as well as the prognosis between GCB and non-GCB types. Forty-two patients with PCNSBLs were included in this study, with 12 (28.6%) classified as GCB type and 30 (71.4%) as non-GCB type. There were no significant differences between the two types in gender, tumor location, or frequency of MYD88^L265P and CD79B^Y196 mutations. Even after consideration of the confounding of age and the presence of R-MPV therapy, the GCB type PCNSBLs tended to exhibit better prognosis. Overall survival tended to be better in those with the GCB/MYD88^L265P mutation (-) group, followed by the GCB/MYD88^L265P mutation (+) group, and the non-GCB type. We speculate that Hans’s algorithm and MYD88^L265P mutation may have potential prognostic value for PCNSBLs.

One-third of the patients with diffuse large B-cell lymphoma (DLBCL) experience relapse despite receiving standard R-CHOP chemotherapy. We aimed to elucidate the clinical course and prognosis in older patients with relapsed or refractory (R/R) DLBCL in a single-center experience in Japan. We conducted a retrospective survey of 52 older patients with R/R DLBCL (aged >65 years at diagnosis; 54% men) who received R-CHOP chemotherapy, to assess their clinical course and prognosis. The median progression-free survival was 8.5 months. Seventeen patients had central nervous system (CNS) relapse, with 11 receiving high-dose methotrexate or whole-brain irradiation. Briefly, 30 patients underwent salvage chemotherapy, whereas 11 received palliative care only. Overall survival (OS) from initial treatment and progression were 20.8 and 7.8 months, respectively. Patients with disease progression within 12 months from initial treatment had a significantly poorer OS than those with disease progression over 12 months, while CNS relapse did not affect OS. Among the 41 reported deaths, 40 were due to lymphoma. As the prognosis in older patients with R/R DLBCL is poor even after salvage chemotherapy, improved initial treatment strategies to reduce the risk of progression and more effective and feasible treatments after progression are warranted.

The prognostic value of models such as the international prognostic index (IPI) in patients with malignant lymphomas treated with a combination of rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone is well established. However, whether these prognostic models apply to patients treated with a combination of tetrahydropyranyl adriamycin, rituximab, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) is unclear. This retrospective analysis included 101 patients with Diffuse large B-cell lymphoma (DLBCL) treated with R-THP-COP. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), complete response rate (CRR), and effectiveness of risk prediction in the IPI, revised international prognostic index (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI groups. OS and PFS at 5 years were 67% and 58.9%. CRR was 63.5%. The IPI, R-IPI, and NCCN-IPI predicted the outcomes of patients treated with R-THP-COP. According to the NCCN-IPI, OS and PFS could distinguish four risk groups. In conclusion, the NCCN-IPI is the most effective prognostic tool for identifying patients with poor prognosis, even those treated with R-THP-COP.

Severe atopic dermatitis (AD) is known to be associated with a risk of lymphoma. We herein report a case of ALK-negative anaplastic large cell lymphoma (ALK-ALCL) complicated by severe AD during treatment with baricitinib, which is an oral, selective, and reversible Janus Kinase (JAK) 1 and 2 inhibitor used in the treatment of AD. Next-generation sequencing (NGS) demonstrated the TP53 p.G266E mutation, suggesting that this was the trigger of the disease and the cause of its refractory course. The JAK/signal transducer and activator of transcription (STAT) pathway is often activated in tumor cells of ALCLs, suggesting that it is a therapeutic target. The causal connection between baricitinib and lymphomagenesis remains unknown; however, this patient developed ALK-ALCL with TP53 mutations during baricitinib treatment.

Intravascular lymphoma (IVL) is a rare subtype of lymphoma, mostly of B-cell origin. A few cases of IVL have been reported as having NK/T cell origins (IVNKTL). These cases are known to be fatal, especially when systemic symptoms are present. We report the case of a patient of IVNKTL who was refractory to initial treatment and received autologous hematopoietic stem cell transplantation (auto-HSCT). She has maintained complete remission (CR) for over eight years. Our case might support the evidence of auto-HSCT for the treatment of IVNKTL with chemosensitivity.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a serious complication observed in patients receiving advanced immunotherapies such as bispecific antibodies and CAR-T cell therapies. Although the Immune Effector Cell-Associated Encephalopathy (ICE) score is commonly used to assess ICANS severity, its diagnostic accuracy can be compromised by factors such as concomitant medications, underlying comorbidities, and other external influences. This case report discusses a patient with diffuse large B-cell lymphoma who developed ICANS while receiving Epcoritamab. Notably, elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF) correlated with the patient’s clinical course of neurotoxicity. In contrast to conventional scoring systems, which can be affected by unrelated factors, CSF IL-6 levels appeared to more directly reflect the severity and progression of ICANS. These findings are consistent with similar reports from patients treated with CAR-T cells, suggesting that CSF IL-6 may serve as a reliable marker for ICANS progression. Further research that systematically measures CSF IL-6 in diverse clinical contexts could help validate its role as a biomarker, enhancing diagnostic precision and guiding optimal management strategies for ICANS.