No comparative analysis of the infrequently occurring B-cell neoplasms (BCNs) in the oral cavity has yet been reported in patients with non-immunosuppressiveness or immunosuppressiveness. To identify any differences in clinicopathological findings between patients with non-immunosuppressiveness and those with immunosuppressiveness, we compared the clinicopathological characteristics of oral-cavity BCNs in these patient groups. The clinical characteristics of 39 patients were analyzed from hospital records, including 24 with non-immunosuppressiveness and 15 with immunosuppressiveness. Histological and immunohistochemical evaluation was performed using formalin-fixed paraffin-embedded tissue sections. Comparisons between the two groups were conducted using cross-tabulations and the chi-squared or Fisher exact test. In patients with non-immunosuppressiveness, diffuse large B-cell lymphoma (DLBCL) was the most common type (14/24, 58%), followed by mucosa-associated lymphoid tissue lymphoma (MALT-L, 4/24, 17%). In patients with immunosuppressiveness, EBV-positive mucocutaneous ulcers (EBV-MCU) were the most common type (9/15, 60%), followed by DLBCL (3/15, 20%) and polymorphic/lymphoplasmacytic infiltration (3/15, 20%). Macroscopic findings showed 21 masses (88%) and 3 ulcers (13%) in patients with non-immunosuppressiveness and 11 ulcers (73%) and 4 masses (27%) in patients with immunosuppressiveness. Immunohistochemistry revealed that BCNs in patients with non-immunosuppressiveness expressed EBER in only 1 case (1/22, 5%), whereas those in patients with immunosuppressiveness expressed EBER in all cases (15/15, 100%). Our macroscopic findings and EBV status allowed us to distinguish BCNs between patients with non-immunosuppressiveness and those with immunosuppressiveness.

Background Brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) has demonstrated survival benefits over cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with CD30-positive peripheral T-cell lymphoma (PTCL) in a randomized, clinical trial. However, data on the real-world effectiveness of BV-CHP in routine clinical practice remain limited.

Methods We conducted a multicenter, retrospective cohort study of patients with newly diagnosed PTCL treated at institutions within the Gifu Hematology Study Group. Patients received BV-CHP, CHOP, or cyclophosphamide, pirarubicin, vincristine, and prednisone (THP-COP) as first-line therapy. Progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) were compared among the treatment groups. Exploratory subgroup analyses were performed, including analyses by bone marrow involvement at diagnosis.

Results A total of 154 patients were included: 29 received BV-CHP, 72 received CHOP, and 53 received THP-COP. Overall, no significant differences were observed in PFS, OS, or ORR among the three treatment groups. In exploratory subgroup analyses, patients with bone marrow involvement who were treated with BV-CHP (n = 4) had significantly shorter PFS than those treated with CHOP (n = 17) or THP-COP (n = 15), whereas no significant difference in OS was observed.

Conclusions In this real-world multicenter cohort from the Gifu Hematology Study Group, frontline BV-CHP did not demonstrate a survival advantage over CHOP or THP-COP in unselected patients with PTCL. These findings suggest that THP-COP remains a reasonable first-line treatment option in routine clinical practice. The inferior PFS observed in patients with bone marrow involvement treated with BV-CHP should be interpreted cautiously and warrants further investigation.

Background Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) has become a first-line treatment option for diffuse large B-cell lymphoma (DLBCL), but real-world data remain limited. We retrospectively compared Pola-R-CHP and R-CHOP in patients with newly diagnosed DLBCL. Methods: We analyzed 127 patients who received first-line Pola-R-CHP (n = 57) or R-CHOP (n = 70) at a single center between January 2021 and August 2025. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events. A 120-day landmark analysis, subgroup analyses, and exploratory analysis for sepsis were also performed. Results: Median age was 75 years in the Pola-R-CHP group and 79.5 years in the R-CHOP group; patients aged >80 years were more frequent in the R-CHOP group (21.1% vs 47.1%, P = 0.003). 1-year PFS was 83.9% with Pola-R-CHP and 76.9% with R-CHOP (P = 0.56). 1-year OS was 89.8% and 91.1%, respectively (P = 0.61). In the 120-day landmark analysis, no significant difference in PFS was observed (HR 0.68, 95% CI 0.29–1.56, P = 0.36). Infection-related treatment discontinuation was more frequent with Pola-R-CHP (12.3% vs 0%, P = 0.003). Sepsis was also more frequent in the Pola-R-CHP group (14.0% vs 4.3%, P = 0.098). Conclusions: In this single-center retrospective cohort, Pola-R-CHP was not associated with a significant improvement in PFS compared with R-CHOP. Infection-related treatment discontinuation was more frequent in the Pola-R-CHP group. Sepsis was also numerically more frequent, highlighting the importance of careful infection monitoring in clinical practice.

Clonality testing using BIOMED-2-based multiplex PCR is widely applied in routine diagnostics, but its interpretation can be complicated by clonal-like peaks arising from non-neoplastic immune responses. In this study, we retrospectively analyzed routine diagnostic cases examined by IGH and TCRB multiplex PCR and assessed both the number of rearranged regions and peak patterns in B-cell lymphoma (N = 291), T-cell lymphoma (N = 48), Classic Hodgkin lymphoma (N = 31), reactive lymphoid hyperplasia (N = 28), and carcinoma (N = 41). The most clinically relevant finding was the frequent detection of apparent IGH clonality in carcinoma, often accompanied by polyclonal background. Clonal IGH peaks were detected in 16 of 35 carcinoma cases (46%), including 7 of 35 cases (20%) with peaks in two or more regions. Among these 16 cases, 11 (69%) showed polyclonal background. In contrast, reactive lymphoid hyperplasia showed much lower IGH positivity, with clonal peaks in 3 of 25 cases (12%) and only 1 of 25 cases (4%) with peaks in two or more regions. More informative than lineage-associated positivity itself were the disease-specific peak patterns, especially the frequent appearance of clonal-like IGH peaks with polyclonal background in carcinoma and the background-rich patterns seen in T-follicular helper cell lymphoma, angioimmunoblastic type/angioimmunoblastic T-cell lymphoma (AITL). These findings indicate that BIOMED-2 clonality assays capture not only neoplastic clones but also disease-specific immune background. Frequent IGH peaks with polyclonal background in carcinoma represent an important diagnostic pitfall and should be interpreted carefully together with the pathological and immunohistochemical results.

Primary mediastinal large B-cell lymphoma (PMBCL) typically responds to chemotherapy, and immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapy and the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab have shown promise in relapsed or refractory cases. However, the sequential use of multiple immunotherapies for PMBCL remains poorly characterized. Here, we report a case of a 19-year-old female with PMBCL involving the mediastinum and multiple extranodal sites. After a partial response to chemotherapy, she developed a central nervous system relapse that responded to high-dose methotrexate, and the number of regrowing mediastinal lesions was reduced by radiotherapy. Subsequently, new hepatic lesions that were refractory to both CAR-T therapy and pembrolizumab emerged. Following localized liver radiotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed, resulting in complete response. Early post-transplant, she developed a hepatitis variant of acute graft-versus-host disease, which may have reflected a graft-versus-lymphoma (GVL) effect. Despite maintaining response, the patient died one year later form a disseminated infection with multitriazole-resistant Aspergillus fumigatus. This case highlights both the potential curative role and the substantial risks of allo-HSCT in PMBCL refractory to multiple immunotherapies. The pre-transplant use of pembrolizumab and localized radiotherapy may influence transplant outcomes and warrants further investigation.

Bone marrow–liver–spleen (BLS)-type diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive variant characterized by primary involvement of the bone marrow, liver, and spleen without lymphadenopathy. We describe the case of a 73-year-old woman who presented with multiorgan failure complicated by disseminated intravascular coagulation and clinical features suggestive of secondary hemophagocytic lymphohistiocytosis. Prompt initiation of intensive chemotherapy (R-CHOP: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone) guided by characteristic clinical findings including bone marrow smear examination, resulted in rapid clinical improvement and prolonged survival.

Rather than representing an unusual diagnostic dilemma, this case illustrates a clinically characteristic and educational presentation of BLS-type DLBCL and highlights the importance of timely lymphoma-directed treatment based on readily available hematologic evidence.

Although the use of bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is expanding, reports of pseudoprogression following this therapy are scarce. A 58-year-old, male patient with DLBCL achieved a complete response (CR) after fourth-line therapy with lisocabtagene maraleucel. However, 26 months post-infusion, he experienced the development of pelvic lymphadenopathy, which was histologically confirmed as a relapse. Because the disease was refractory to radiotherapy and chemotherapy, epcoritamab was administered as the seventh-line treatment. A fever developing after the second step-up dose (Cycle 1, day 12) was diagnosed as grade 1 cytokine release syndrome and was treated with acetaminophen. Nonetheless, the fever was still present on day 14, when abdominal pain requiring opioid administration also developed. Computed tomography (CT) revealed enlargement of the pelvic lesions and increased ascites. Cytology of the ascites revealed no lymphoma cells and showed a predominantly inflammatory cell composition, while lactate dehydrogenase levels decreased, supporting the diagnosis of pseudoprogression. The treatment was continued and his symptoms gradually improved. After three cycles, positron emission tomography-CT confirmed the complete metabolic response (CMR), which was maintained through nine cycles. The present case highlights the potential for pseudoprogression to occur during epcoritamab therapy, suggesting that continued treatment may lead to durable remission even in patients with early clinical deterioration.

Adult T-cell leukemia/lymphoma (ATL) is a rare T-cell malignancy, where the chronic type often progresses to an acute form in the presence of poor prognostic factors. We report a remarkable case of chronic-type ATL that achieved long-term hematologic and molecular remission following methimazole treatment for concomitant Graves’ disease. A 58-year-old woman was diagnosed with chronic-type ATL in 2022. Her disease showed gradual progression with elevated soluble interleukin-2 receptor (sIL-2R) levels and lactate dehydrogenase. In 2023, she developed Sjögren’s syndrome and Graves’ disease. Following the initiation of methimazole for hyperthyroidism, her abnormal lymphocyte counts and sIL-2R levels unexpectedly and rapidly decreased. She has maintained clinical stability for over two years without any cytotoxic chemotherapy. Multi-color flow cytometry confirmed the disappearance of the CD4+/CADM1+/CD7− ATL cell population in the peripheral blood. Furthermore, longitudinal genomic profiling using Target-seq revealed a significant reduction in the variant allele frequencies of major driver clones, including a PDCD1 frameshift mutation, and a shift from monoclonal expansion to a polyclonal HTLV-1 carrier state. This case provides the first clinical evidence of a potential anti-ATL effect of methimazole and underscores the importance of the endocrine-immune axis in HTLV-1–associated malignancies, warranting further investigation into antithyroid therapy as a novel treatment strategy for indolent ATL.

CD20 testing shortly after CD20-directed therapy can be difficult to interpret. We report an 89-year-old woman with multiply relapsed B-cell lymphoma who underwent excisional biopsy of an enlarging right axillary lymph node 17 days after the last dose of mosunetuzumab. A prior lymph node biopsy showed follicular lymphoma grade 3A with preserved CD20 expression. The relapse specimen showed diffuse large B-cell lymphoma of the germinal center B-cell subtype. Immunohistochemistry using the CD20 clone L26 failed to detect CD20 expression, whereas PAX5 and CD79a remained positive. Flow cytometry showed undetectable CD20 with clone L27; the large-cell gate contained CD19-positive B cells and showed kappa light-chain restriction. No morphologic findings of a lineage switch were observed. IGH and IGK rearrangement analyses demonstrated identical monoclonal peaks in the specimens obtained at the follicular lymphoma stage and relapse, supporting clonal continuity. Positron emission tomography/computed tomography revealed a 40-mm right axillary lymph node with a maximum standardized uptake value of 26.7. Epcoritamab was started as the seventh-line treatment despite negativity on routine assays for CD20. During step-up dosing, grade 1 cytokine release syndrome resolved after one dose of tocilizumab. Computed tomography on day 22 revealed a reduction in the size of the right axillary lymph node from 40 to 20 mm. The lesion remained 20 mm on days 41 and 51, with decreases in lactate dehydrogenase and soluble interleukin-2 receptor. Disease progression was documented on day 83. These findings suggest that negative CD20 results by routine assays shortly after mosunetuzumab therapy do not necessarily reflect true target loss. Integrated interpretation of histopathology, flow cytometry, and clonality studies may help guide subsequent CD20-directed treatment decisions.

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, renal dysfunction, and myelofibrosis, and its follows a rapidly fatal clinical course. A few cases of TAFRO syndrome complicated by adrenal hemorrhage were recently reported; however, its pathogenetic significance remains largely unclear.

The present case was a 59-year-old man presenting with left lower back pain. Imaging studies revealed left adrenal hemorrhage. Although an elevated C-reactive protein level was observed in the initial visit, there were no obvious abnormalities in the platelet count, renal function, or coagulation profile. Subsequently, fluid retention and renal dysfunction progressed rapidly, and thrombocytopenia emerged, leading to a diagnosis of TAFRO syndrome. Treatment including glucocorticoid therapy was initiated, but was ineffective; the disease progressed rapidly, and the patient succumbed to multiple organ failure. Autopsy revealed findings consistent with TAFRO syndrome in small lymph nodes and those suggestive of thrombotic microangiopathy in renal glomeruli.

Based on these findings, adrenal hemorrhage may occur as an initial presentation prior to the manifestation of the full systemic picture of TAFRO syndrome. Furthermore, the disease progressed rapidly to a severe state in a short period without initial thrombocytopenia—which complicated the diagnosis—and demonstrated resistance to conventional treatments including glucocorticoids, which underscores the importance of early recognition and therapeutic intervention.

Hemophagocytic lymphohistiocytosis (HLH) complicating classic Hodgkin lymphoma (HL-HLH) is a rare but frequently life-threatening condition that is strongly associated with Epstein–Barr virus (EBV) infection, particularly in the mixed-cellularity and lymphocyte-depleted subtypes. No consensus has been reached regarding treatment for HL-HLH, and the myelotoxicity induced by etoposide-based HLH-directed therapy precludes its safe addition to intensive lymphoma-directed chemotherapy, particularly in older patients. We here report the case of a male in his early 70s with advanced EBV-positive mixed-cellularity classic Hodgkin lymphoma (CHL) who presented with cervical lymphadenopathy, fever, hepatosplenomegaly, and a markedly elevated soluble interleukin-2 receptor (sIL-2R) level, along with a high peripheral blood EBV DNA load. EBV-encoded small RNA in situ hybridization confirmed EBV positivity in lymphoma cells. His fever was steroid-refractory, and chemotherapy with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (BV-AVD) was initiated immediately following the diagnosis was confirmed. However, the persistent high fever did not resolve, and progressive cytopenia, marked hyperferritinemia, and further increase in sIL-2R levels were observed. Repeat bone marrow examinations revealed macrophage activation with hemophagocytosis, confirming HLH as a complication. Rituximab was promptly administered, and the fever resolved within 3 days. Furthermore, ferritin, sIL-2R, and lactate dehydrogenase levels substantially declined within 1 week, with peripheral blood EBV DNA becoming undetectable. BV-AVD was continued without major complications and led to a complete response after six cycles. Rituximab may represent a strategically timed and reasonable adjunctive intervention for EBV-driven HL-HLH that is refractory to, or develops following, chemotherapy for CHL.

Pulmonary lesions that newly emerge after chimeric antigen receptor T-cell therapy may raise immediate concern for lymphoma relapse, especially when they occur at sites of prior disease involvement. We report a patient with refractory diffuse large B-cell lymphoma who developed newly apparent or re-enlarged FDG-avid pulmonary opacities four months after axicabtagene ciloleucel infusion. The lesions appeared at or near prior pulmonary lymphoma-suspected sites, strongly suggesting recurrence. However, transbronchial lung biopsy showed organizing pneumonia-like inflammatory changes with Masson bodies, CD3-positive T-cell infiltration, and no evidence of lymphoma involvement by multiple B-cell markers. Because the patient remained clinically stable and relapse was not supported histologically, systemic corticosteroids and salvage chemotherapy were withheld. The biopsied lesion and the remaining pulmonary opacities regressed spontaneously during follow-up, and complete remission was maintained. This case illustrates that organizing pneumonia-like inflammatory lesions may arise at prior lymphoma-suspected pulmonary sites after CAR-T-cell therapy and closely mimic pulmonary relapse on FDG-PET/CT. When new FDG-avid pulmonary lesions arise after CAR-T-cell therapy, particularly at prior lymphoma sites, tissue confirmation is essential to avoid misdiagnosis and unnecessary treatment escalation.