Human T-cell leukemia virus type 1 (HTLV-1) causes persistent infection and can lead to adult T-cell leukemia-lymphoma (ATL), a hematological malignancy with a poor prognosis. In ATL patients, monoclonal expansion of HTLV-1-infected cells is observed. Each HTLV-1-infected clone harbors a unique proviral integration site. Based on this feature, various methods have been developed to detect and characterize HTLV-1-infected clones. Traditional Southern blotting detects monoclonal proliferation; however, it lacks sensitivity for detecting minor clones. Polymerase chain reaction (PCR)-based approaches, including inverse PCR and linker-mediated PCR, enhance sensitivity and can detect clonal proliferation even in asymptomatic carriers. The advent of high-throughput sequencing has enabled high-resolution quantitative analysis of the clonality of HTLV-1-infected cells based on proviral integration sites. Additionally, HTLV-1 DNA capture-seq allows simultaneous identification of the proviral structure and the degree of clonal abundance of the expanded infected clones. The modified non-restrictive linear amplification-mediated PCR and sequencing is a rapid and cost-effective tool for integration site analysis that is suitable for clinical application. These approaches could help analyze HTLV-1 pathogenesis, monitor clonal dynamics, and improve patient care strategies.

BTK inhibitors (BTKi) are established standards of care for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL); however, their use has been associated with an increased risk of bleeding. We investigated whether BTKi impaired platelet aggregation and adhesion in a drug- or dose-dependent manner in patients with CLL and MCL who received ibrutinib, acalabrutinib, or pirtobrutinib. Treatment with BTKi significantly inhibited 2 µg/mL collagen-induced platelet aggregation (CIPA) by 82.1±7.3% (P < 0.0001) in maximum aggregation rates, with levels independent of BTK selectivity and the applied dose. This inhibitory effect was more potent than that of acetylsalicylic acid (aspirin, 100 mg daily) (P < 0.0001). BTKi did not significantly affect adenosine diphosphate- or ristocetin-induced aggregation. The first-generation BTKi ibrutinib but not the newer BTKi acalabrutinib or pirtobrutinib, impairs platelet adhesion, possibly owing to the different inhibitory profiles to SRC family kinases. Our findings have two clinical implications. First, because BTKi treatment inhibits CIPA as a class effect, independent of drug specificity or dose, measuring CIPA levels alone may not help physicians predict near-future bleeding complications. Although the sample size was small, our results suggest the potential of impaired platelet adhesion as a candidate biomarker for estimating bleeding risk in patients receiving BTKi. Second, in BTKi-treated patients requiring anti-platelet agents, BTKi dose reduction may be considered, irrespective of BTK selectivity of the drug or whether aspirin or a P2Y_¹² receptor inhibitor is used.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus-1. Patients diagnosed with aggressive ATL have a poor prognosis. As response duration to conventional multiagent chemotherapy is short, upfront allogeneic hematopoietic cell transplantation (allo-HCT) is recommended. As disease status at the time of allo-HCT is the primary prognostic factor, bridging therapy to allo-HCT is sometimes necessary during donor coordination. However, conventional chemotherapies are often toxic, particularly for older patients and those with inadequate hematopoietic recovery. Anti-CCR4 monoclonal antibody mogamulizumab adversely affects post-transplant survival due to the high risk of severe graft-versus-host disease (GVHD). Available data on other novel agents for ATL are limited. The present case study details an ATL patient who exhibited chemotherapy intolerance, but was successfully bridged to unrelated peripheral blood stem cell transplantation (uPBSCT) with valemetostat, a selective dual inhibitor of enhancer of zeste homolog 1 and 2. Despite severe bone marrow failure, valemetostat was well tolerated by the patient and led to successful disease control prior to uPBSCT, which is considered to have contributed to a reduced risk of post-transplant relapse and an improved prognosis. No significant adverse effects of valemetostat were observed early after transplantation, in contrast to the increased incidence of severe GVHD and non-relapse mortality reported following allo-HCT after mogamulizumab therapy. These findings suggest that valemetostat is a promising option as a bridging therapy to allo-HCT for aggressive ATL.

Multiple myeloma (MM) is a marrow-based, multi-focal neoplastic proliferation of clonal plasma cells. Myelomatous pleural effusion (MPE) is considered a distinctive form of extramedullary disease and usually develop in disease progression or recurrence, but rarely at initial disease presentation of MM. Herein we report a 47-year-old male patient with MM who presented initially with MPE. The typical cytological features (eccentric nuclei and amphophilic cytoplasm with paranuclear hof), flow cytometric immunophenotyping, and cell block preparation with immunohistochemistry confirmed MPE. After establishing the diagnosis of stage III myeloma through bone marrow study, laboratory and radiological corrections, the patient was treated with chemotherapy and palliative radiotherapy. Unfortunately his disease progressed and he passed away in six months. Our case illustrated the importance of detailed cytological examination with ancillary studies for the challenging diagnosis of an extremely rare initial disease presentation of MM with MPE, which is an ominous sign.

Most primary testicular malignant lymphomas are derived from B-cell, with only a few cases of T-cell origin (primary testicular T cell lymphoma; PTTCL). In this report, we present a case of PTTCL who relapsed simultaneously in the central nervous system (CNS) and peripheral nerves, which was managed by allogeneic hematopoietic stem cell transplantation, but recurred again in the CNS. Treatment with the purine nucleotide phosphorylase inhibitor Forodesine achieved a therapeutic response. This finding suggests that Forodesine might be useful as a treatment option for CNS relapse in heavily treated T-cell lymphoma.

IgM-related AL amyloidosis is a rare and distinct clinical entity, often associated with underlying lymphoproliferative disorders such as Waldenström’s macroglobulinemia (WM) or lymphoplasmacytic lymphoma (LPL). Unlike non-IgM AL amyloidosis, it exhibits unique organ involvement patterns and generally poorer prognosis. We report a 66-year-old woman diagnosed with WM complicated by systemic IgM-κ AL amyloidosis. She received combination chemotherapy with rituximab and bendamustine (BR), resulting in a reduction of serum IgM levels. Despite the hematologic improvement, her liver dysfunction rapidly progressed, and she died of hepatic failure just two months after diagnosis. Pathological autopsy revealed massive IgM-κ amyloid deposition in the liver and multiple organs, with no residual lymphoma in the bone marrow or lymph nodes. These findings suggest that extensive hepatic amyloid infiltration was already present at diagnosis, and that organ response could not be achieved despite hematologic improvement. This case highlights the aggressive nature of IgM-related AL amyloidosis and the critical importance of early detection, especially when liver dysfunction is observed. Current therapies targeting the underlying clone may not be sufficient in cases with advanced organ involvement, emphasizing the urgent need for novel strategies to facilitate amyloid clearance and protect organ function.

Epstein-Barr Virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV-IFDCS) is a rare tumor of low malignant potential. Abundant lymphocytes and plasma cells often infiltrate into this tumor tissue with lymphoid follicles and sarcoid-like granulomas, so that the differential diagnosis of this tumor includes inflammatory lesions such as IgG4-related disease, morphologically. This tumor typically arises in the spleen or liver, and shows follicular dendritic cell (FDC)-like immunophenotype. Here we presented a case of EBV-IFDCS arising in intrapancreatic accessory spleen, which was preoperatively considered as a pancreatic tumor. Immunohistochemistry revealed its fibroblastic reticular cell-like phenotype, namely alpha SMA, l-caldesmon, tenascin C, and transglutaminase II positivity, while FDC marker expression such as CD21 and clusterin was focal. Positivity for EBV-encoded small RNA in situ hybridization (EBER ISH) distinguished it from inflammatory lesions or conventional FDC sarcoma. The differential diagnosis of EBV-IFDCS is broad, ranging from non-neoplastic lesions to sarcoma, particularly when it arises in unusual sites. Therefore, careful gross and microscopic examination and adequate immunohistochemistry application including EBER ISH are important to diagnose it properly.

Non-Waldenström macroglobulinemia (non-WM) lymphoplasmacytic lymphoma (LPL) is a rare subtype with limited clinical evidence and no confirmed treatment guidelines. Bruton tyrosine kinase (BTK) inhibitors represent one of the mainstay therapies in WM, but their role in non-WM LPL remains unclear. We report a case of IgG-type non-WM LPL successfully treated with a second-generation BTK inhibitor, tirabrutinib. The patient demonstrated a rapid decline in M-protein and improvement in anemia, with a durable partial response. This case adds to the limited literature supporting BTK inhibitor use in non-WM LPL and highlights the need for further studies to define optimal treatment strategies.

Infectious complications are common following chimeric antigen receptor (CAR) T-cell therapy for B-cell lymphoma due to its prolonged immunosuppressive effects. Schizophyllum commune is an exceedingly rare fungal pathogen that typically affects the respiratory tract and may mimic chronic pulmonary aspergillosis. Infections caused by S. commune have been primarily reported in recipients of allogeneic hematopoietic stem cell transplantation. Here, we report the first known case of S. commune infection in a patient treated with CAR T-cell therapy. A 71-year-old woman with primary refractory large B-cell lymphoma received lisocabtagene maraleucel as second-line therapy. Six months post-treatment, computed tomography revealed right middle lobe atelectasis with high-attenuation mucus. Bronchoscopic biopsy, fungal culture, and internal transcribed spacer gene region sequencing confirmed the diagnosis of S. commune infection presenting as allergic bronchopulmonary mycosis (ABPM). Notably, serologic tests were negative for fungus-specific specific immunoglobulin G and immunoglobulin E. The patient responded favorably to 4 months of oral voriconazole therapy, with resolution of symptoms and radiologic findings. This case highlights the potential for rare fungal infections, such as S. commune, to occur following CAR T-cell therapy. Although the clinical and radiologic features were consistent with ABPM, the absence of serologic markers underscores the diagnostic challenges posed by B-cell aplasia resulting from B-cell-directed immunotherapy.