Tirabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, was approved in Japan in August 2020 for the treatment of Waldenström’s macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL). We report the findings of post-marketing surveillance (PMS) of tirabrutinib that was started following its approval. We conducted an all-case PMS of patients who started tirabrutinib treatment between August 21, 2020, and January 17, 2021, for WM/LPL in Japan. Safety and effectiveness data were recorded for up to 52 weeks after the first dose of tirabrutinib. Among 152 patients who started tirabrutinib, 67.1% were male, 77.6% were ≥ 65 years old, and 61.8% started treatment with tirabrutinib at 480 mg/day (once-daily). Among these 152 patients, any-grade and grade ≥ 3 adverse drug reactions (ADRs) occurred in 58.6% and 29.6% of patients, respectively. The main ADRs were platelet count decreased (9.2%) and rash (9.2%). Grade 5 ADRs were reported in four patients (2.6%). The outcomes of most ADRs associated with the safety specifications (myelosuppression, infections, interstitial lung diseases, clinically significant skin disorders, hemorrhages, hepatic function disorders, and hypersensitivities) were resolved or improved. The effectiveness was assessed by the physicians using the VIth International Workshop for Waldenström’s Macroglobulinemia criteria. Among 85 patients (initial dose: 480 mg/day) included in the effectiveness analysis set, the major response and overall response rates were 63.5% and 74.1%, respectively. This PMS suggested that the safety profile of tirabrutinib for patients with WM/LPL in real-world clinical settings is in line with that observed in prior studies.

Nodal T-follicular helper cell lymphoma (nTFHL) may present with Hodgkin/Reed–Sternberg (HRS)-like cells and can morphologically mimic classic Hodgkin lymphoma (CHL), although these entities are usually distinguishable. We report an unusual case showing marked morphologic and molecular overlap with CHL, creating a diagnostic challenge but ultimately considered biologically consistent with nTFHL.

An 81-year-old woman presented with stage IV disease involving the bone marrow and markedly elevated serum soluble interleukin-2 receptor levels. Excisional lymph node biopsy revealed scattered HRS cells in a T-cell–rich background, with strong CD30 and PD-L1 expression and weak PAX5 positivity, findings consistent with CHL. Fluorescence in situ hybridization demonstrated copy-number alterations at the 9p24.1 locus in HRS cells, further supporting molecular features characteristic of CHL.

However, the presence of two T-follicular helper markers, detection of the RHOA p.Gly17Val (G17V) mutation, and oligoclonal T-cell receptor rearrangements with shared peaks in lymph node and bone marrow indicated an underlying nTFHL. The differential therapeutic response also supported a diagnosis of nTFHL, which could not have been established on morphology alone.

In this case, although the HRS cells displayed morphological, immunophenotypic, and molecular features highly suggestive of CHL, the biological nature of the lesion was consistent with nTFHL. Compared with previously reported cases of nTFHL with HRS-like cells, this case more closely resembled CHL and may represent a distinct subset best described as “nTFHL with CHL features,” a concept warranting greater recognition among pathologists and clinicians.

We report a case of adult T-cell leukaemia/lymphoma (ATLL) that exhibited different pathological subtypes within a single lymph node. The patient was a 76-year-old Japanese man who presented with decreased appetite and anemia, and a thorough examination was conducted. A peripheral blood analysis and imaging studies, including ultrasound and computed tomography, suggested malignant lymphoma, and cervical lymph node biopsy was subsequently performed.

In the excised lymph node, the normal architecture was completely effaced, and areas showing the dense proliferation of pleomorphic atypical lymphocytes—consistent with the most common histology of ATLL (pleomorphic cell variant)—were identified. Regions exhibiting features reminiscent of classic Hodgkin lymphoma and others resembling angioimmunoblastic T-cell lymphoma were also observed. Serological testing was positive for human T-lymphotropic virus type 1 antibodies, and together with histological findings, this case was diagnosed as ATLL.

To the best of our knowledge, there have been no cases exhibiting different histological patterns within a single lymph node.

Diffuse large B-cell lymphoma (DLBCL) can occur at various sites and is rarely diagnosed as synchronous multiple primary malignancies. A treatment approach for this synchronous malignancy has not been established. Here, we report two cases of synchronous DLBCL and gynecological malignancy treated with the paclitaxel and carboplatin (TC) regimen. Patient #1: A 67-year-old female presented with right axillary lymphadenopathy. A computed tomography (CT) revealed a hepatic mass and an ovarian tumor. Biopsy of the lymphadenopathy diagnosed DLBCL (stage I). Ovarian and peritoneal biopsies confirmed ovarian cancer (stage IVB, peritoneal dissemination, and liver metastasis). She received 6 cycles of TC chemotherapy for ovarian cancer, followed by surgery (pT3cN0M1) and an additional 2 cycles of TC. A complete metabolic response (CMR) of both malignancies was confirmed 1 year later. Patient #2: A 77-year-old female presented with left knee discomfort. Biopsy of a left femoral tumor diagnosed DLBCL (stage I). PET-CT revealed abnormal fluorodeoxyglucose uptake in the left femur and in the uterus, with an endometrial biopsy confirming endometrial cancer. She received radiation therapy for DLBCL, followed by surgery for endometrial cancer (pT1bNxM0). Postoperatively, 6 cycles of TC chemotherapy were performed, and she achieved a CMR. No Grade 3/4 nonhematologic adverse events were observed in both patients. In conclusion, the TC regimen was safely administered in our two patients. In one of them, TC therapy alone was effective for DLBCL. The clinical courses may provide a valuable reference for the management of similar patients.

Acute promyelocytic leukemia (APL) arising during the clinical course of BCR::ABL1–positive chronic myeloid leukemia (CML) is rare and may represent either promyelocytic blast phase or the emergence of an independent Philadelphia chromosome–negative clone. We report an octogenarian man with chronic-phase CML who was intolerant to multiple tyrosine kinase inhibitors and underwent temporary discontinuation of asciminib. During molecular relapse, bone marrow examination revealed 88% abnormal promyelocytes with Auer rods and markedly elevated PML::RARA transcripts, whereas BCR::ABL1 transcript levels were more than 3 logs lower than at CML diagnosis. Conventional cytogenetics demonstrated t(15;17) without t(9;22) as the dominant clone, supporting de novo APL arising independently of the residual CML clone. All-trans retinoic acid plus arsenic trioxide achieved molecular remission of PML::RARA and was followed by an initial marked reduction in BCR::ABL1 transcript levels, which subsequently remained detectable at low levels during continued follow-up. This case highlights the importance of integrated cytogenetic and molecular evaluation to distinguish blast phase from independent leukemogenesis in patients with CML who develop cytopenias.

Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of B-cell lymphoma associated with immunodeficiency and Epstein–Barr virus (EBV) infection. Although PBL can develop from indolent lymphomas, its occurrence long after diffuse large B-cell lymphoma (DLBCL) is rare. A 67-year-old man was diagnosed with EBV-positive DLBCL 17 years ago and achieved a sustained remission following six cycles of R-CHOP therapy. Seventeen years after the initial DLBCL diagnosis, the patient developed PBL with EBV-positive tumor cells. After three cycles of EPOCH therapy, the patient achieved a partial response and underwent upfront autologous stem cell transplantation, resulting in complete remission. To investigate the clonal relationship between DLBCL and PBL, immunoglobulin gene repertoire analysis using next-generation sequencing was performed on both specimens. In the PBL specimen, immunoglobulin heavy chain rearrangement revealed a dominant clone with a complementarity-determining region 3 (CDR3) length of 38 amino acids. Although the DLBCL specimen lacked a dominant clone meeting the clonality criteria, a minor clone with a CDR3 sequence similar to that of the PBL dominant clone was detected. This clone exhibited an unusually long CDR3 sequence (37 amino acids), likely contained stop codons, and was considered a nonfunctional clone. These findings suggest that PBL originated through expansion of a pre-existing minor subclone that persisted since the initial DLBCL diagnosis, driven by long-term clonal dynamics. Our case highlights the potential utility of immunoglobulin repertoire analysis in identifying clonal relationships among lymphomas, supporting treatment decisions, and understanding the pathogenesis of secondary lymphomas.

Histiocytic sarcoma (HS) is a rare, aggressive malignant neoplasm characterized by histiocytic features, frequently presenting in advanced clinical stages and associated with a poor prognosis. Although HS can occur sporadically or secondary to other hematological malignancies, cases with a long latency period have been rarely reported. This case report presents a unique case of secondary HS diagnosed 33 years and seven months after the initial diagnosis of B-cell precursor acute lymphoblastic leukemia. Both neoplasms shared identical immunoglobulin heavy chain and T-cell receptor gene rearrangements, confirming a clonal relationship. To the best of our knowledge, this case represents the longest reported interval between primary leukemia and secondary HS, highlighting the potential for lineage switching and transformation over extended periods. These findings underscore the need for ongoing research on the mechanisms underlying “transdifferentiation”, including the roles of transcription factors, cytokine signaling, and epigenetic modifications.

Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma characterized by a relapsing clinical course. Recently, CD20×CD3 bispecific antibodies, including mosunetuzumab, have emerged as effective therapeutic options for relapsed or refractory FL. However, their efficacy in malignant effusions, including pleural effusion, remains unclear. We report a case of relapsed FL complicated by chylothorax that showed a rapid response to mosunetuzumab. A 74-year-old woman with a history of FL, initially treated with R-CHOP and later with rituximab monotherapy, presented with progressive dyspnea and was found to have bilateral pleural effusion. Analysis of pleural fluid revealed chylothorax with infiltration of CD20-positive lymphoma cells, confirmed by flow cytometry and cell-block immunohistochemistry. Following initiation of mosunetuzumab, pleural effusion decreased promptly, with a marked reduction in lymphoma cells in the pleural fluid observed as early as day 2. The patient achieved a complete metabolic response on positron emission tomography–computed tomography (PET-CT) after eight cycles of therapy. This case suggests that mosunetuzumab may exert rapid antitumor activity in both systemic disease and malignant effusions, possibly through distribution into pleural fluid and subsequent T-cell–mediated cytotoxicity. Further studies are warranted to clarify the role of bispecific antibodies in malignant effusions associated with lymphoma.