Background Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis that responds well to glucocorticoid therapy. However, some patients experience frequent relapses or become glucocorticoid-dependent. In Western countries, immunosuppressive agents such as azathioprine are widely used to maintain remission. In contrast, evidence for the use of immunosuppressive agents for AIP is limited in Japan and other Asian countries. Therefore, this study aimed to evaluate the efficacy and safety of immunosuppressive agents in patients with refractory AIP. Methods We retrospectively analyzed 12 Japanese patients with type 1 AIP who experienced two or more documented relapses and received immunosuppressive therapy. Clinical remission, adverse events, and the incidence of malignancy were assessed. Results Among 199 patients with AIP treated between 2006 and 2024, 12 (6.0%) with multiple relapses were administered immunosuppressive agents, including azathioprine (n=9), tacrolimus (n=2), and methotrexate (n=1). Nine patients continued therapy for at least two months; of these, eight (88.9%) maintained clinical remission without relapse during treatment. One patient relapsed. However, three patients (25.0%) were unable to continue therapy due to adverse events. Two patients developed malignancies during the long-term follow-up: one with malignant lymphoma and the other with small cell lung cancer. Conclusion Immunosuppressive therapy may contribute to the maintenance of remission in some AIP patients with glucocorticoid-dependent or repeated relapses, even among Japanese patients. However, adverse events led to treatment discontinuation in 25% of patients, and two developed malignancies during follow-up. These findings underscore the need for careful patient selection, individualized risk-benefit evaluation, and ongoing monitoring.

The UL23 thymidine kinase of Marek's disease virus is a target for anti-HSV drug development.

Peripheral neuropathy is rarely the initial presentation of lymphoma. Acute inflammatory demyelinating sensorimotor neuropathy, meeting the diagnostic criteria of Guillain-Barré syndrome, might be associated with Hodgkin’s lymphoma. A 33-year- old woman presented with dyspnea, generalized lymphadenopathy, acute-onset progressive ascending muscle weakness of the lower extremities, and acute bilateral uveitis. EMG-NCV confirmed acute inflammatory demyelinating polyneuropathy. Malignant lymphoma was suspected. A core needle biopsy of the left axillary lymph node was performed and revealed the classic type of Hodgkin’s lymphoma. The ABVD regimen was administered along with five consecutive sessions of plasmapheresis. The neurological signs and symptoms improved gradually. In conclusion, acute inflammatory demyelinating polyneuropathy mimicking Guillain-Barré syndrome might be associated with HL and precede the diagnosis of lymphoma. Therefore, clinicians need to be aware of the neurological manifestations of lymphoma for appropriate diagnosis and treatment.

CT attenuation value is useful in the differential diagnosis of adrenal masses, and values <10 Hounsfield units (HU) can exclude malignancy and pheochromocytoma. However, few reports have examined the reliability of CT attenuation measurements. We examined the reliability of CT attenuation measurements made by surgeons not specialized in image reading. A retrospective analysis of 313 patients (325 lesions) who underwent surgery at a single institution was performed. One general surgeon and one endocrine surgeon independently measured CT attenuation values. The intraclass correlation coefficient and Cohen's kappa coefficient were used to analyze interobserver reliability. All cases were subjected for endocrine function tests and histopathologically diagnosed. Additional analyses included segmented regression for size-related measurement variability and multivariable analyses comparing aldosterone-producing adenomas (APAs) and cortisol-producing adenomas (CPAs). The intraclass correlation coefficient between observers was 0.938 (95% CI: 0.923-0.949), and Cohen's kappa coefficient was 0.851 (95% CI: 0.781-0.922). Both observers measured all malignant adrenal tumors (such as adrenocortical carcinoma, metastatic adrenal carcinoma, and malignant lymphoma) and pheochromocytomas as ≥ 10 HU. CT attenuation values were significantly higher in CPAs than in APAs, independent of mass size (P < 0.001 for both observers). CT attenuation value was shown to be reliable enough for simple measurements that could be performed by non-radiologists and was useful for excluding malignancy and pheochromocytoma. This study reinforced evidence for the reliability of CT attenuation value. Even with a simple method that can be performed by non-radiologists, CT attenuation values were highly reliable and useful for excluding malignancy and pheochromocytoma. In addition, all lesions in this study were evaluated both endocrinologically and pathologically, giving high validity to the reference standard. These findings complement and further substantiate the latest clinical practice guidelines of the European Society of Endocrinology.

Adult T-cell leukaemia/lymphoma (ATL) is a malignancy of mature peripheral T-lymphocytes caused by human T-cell lymphotropic virus type I (HTLV-I). Administering conventional chemotherapeutic regimens used against malignant lymphomas to patients with ATL results in poor therapeutic outcomes. Previously, we isolated withanolides from the aerial parts of Physalis pruinosa and observed potent activity against leukaemia cell lines. The most effective compound showed selective toxicity against HTLV-1-infected T-cell lines compared with normal peripheral blood mononuclear cells following analysis of the structure–activity relationship. Here, we isolated 25 compounds from P. pruinosa, including 3 new compounds, and examined their antiproliferative activity against ATL-related cell lines. The EC50 of withanolide E (compound 16) for MT-1 and MT-2 was 28 nM and 37 nM, respectively, which was more potent than etoposide. Additionally, compound 16 induced apoptosis, as shown by annexin V-positive cells and cleaved caspase-3.

Haematological manifestations of immunoglobulin (Ig)G4-related disease (IgG4-RD) are atypical, and few studies have addressed cytopenia in this condition. We present here a case of IgG4-RD with marked pancytopenia and splenomegaly in the absence of bone marrow abnormalities. A 67-year-old woman developed diplopia, dyspnoea, pancytopenia, and hypocomplementemia. Contrast-enhanced computed tomography showed bilateral lacrimal and submandibular gland swelling, enlargement of the cervical, mediastinal, inguinal, and para-aortic lymph nodes, splenomegaly, and granular shadows in both lungs. She had been referred to our hospital on suspicion of malignant lymphoma, but a lymph node biopsy indicated the possibility of IgG4-RD. A lacrimal gland biopsy showed infiltration of numerous lymphocytes and IgG4-positive plasma cells along with mild fibrosis. A bone marrow biopsy showed normocellular marrow with no increase in plasma cells. The IgG4-positive plasma cell count was 4 per high-power field, with an IgG4/IgG ratio of 10%. After excluding potential mimics, the diagnosis was IgG4-RD presenting with pancytopenia and splenomegaly. Prednisolone was initiated at 40mg/day, leading to the rapid normalisation of pancytopenia, recovery of complement levels, and resolution of other organ involvement such as splenomegaly. Physicians should keep in mind that IgG4-RD can present with pancytopenia and splenomegaly.

A 60-year-old Japanese man developed a protruding right eye. He underwent a magnetic resonance imaging scan, which revealed a right orbital mass. The serum immunoglobulin G4 (IgG4) level was elevated, and IgG4+ plasma cells were observed in biopsy specimens of the mass. The result of biopsy and Southern blot analysis revealed that the mass was caused by IgG4+ extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. He received a total of 36Gy of radiation therapy, and the mass disappeared. Five years later, he developed a protruding left eye. The magnetic resonance imaging scan at that time revealed a left orbital mass. Biopsy revealed findings of IgG4-related disease in the left orbital mass, but no findings of mucosa-associated lymphoid tissue lymphoma. He has been followed up without glucocorticoid treatment. Here, we report a patient who developed IgG4+ MALT lymphoma in the right orbital mass and IgG4-related ophthalmic disease in the left orbital mass. Because the treatment strategy for IgG4-related ophthalmic disease and malignant lymphoma is completely different, we emphasise the need for biopsy.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with a poor prognosis. Lymphomatous serous effusion, defined as the presence of malignant lymphoma cells in the pleural, pericardial, or peritoneal fluid, is a rare but clinically important manifestation, particularly when a lymph node biopsy is difficult or delayed. We performed a narrative review of case reports and a small series of AITL cases with lymphomatous effusion, focusing on the clinical presentation, cytologic features, ancillary studies, and outcomes. Reported patients are typically older adults with advanced-stage disease; effusions are usually exudative, of low volume, and cytologically tumor-cell-poor but inflammation-rich; therefore, atypical T follicular helper (TFH)-type T cells are easily overlooked or misclassified. Immunocytochemistry (ICC) on cell block or cell-transfer preparations, flow cytometry, and EBER in situ hybridization improve the recognition of the AITL phenotype, whereas next-generation sequencing (NGS) can detect hallmark mutations such as RHOA G17V, TET2, DNMT3A, and IDH2 directly from effusion samples, enabling a less invasive diagnostic approach when tissue is not readily available. According to previous reports, lymphomatous effusion, which is frequently measured in months, is associated with a short survival. Based on these data and current World Health Organization (WHO) and National Comprehensive Cancer Network (NCCN) guidance, we propose a practical fluid-based diagnostic algorithm that integrates cytology, ancillary tools, and lymph node biopsy when feasible, and we highlight the need for standardized effusion-based workflows, multicenter registries, and the integration of liquid biopsies, multiomics, and artificial intelligence-assisted cytology to refine risk stratification and guide therapy in this distinct subgroup.

ABSTRACTA 62‐year‐old man with right upper quadrant pain and fever was found to have numerous hepatic masses. Endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) using a 22‐gauge fine‐needle biopsy enabled diagnosis of high‐grade T‐cell lymphoma without adverse events. This case underscores the potential of EUS‐TA as a safe and effective alternative to percutaneous biopsy for hepatic malignant lymphoma.

ABSTRACT Lymphoma is commonly considered as cancer that affects the entire organs of the body. The accurate classification of malignant lymphomas is helpful for providing better treatment plans to patients. Usually, the lymphoma types are differentiated by cytologic features and growth patterns. Moreover, the abnormal cell variations are effectively identified through the immunologic, genetic, and clinical features that are useful in making the diagnosis. The gap between pattern analysis and cancer diagnostics is effectively handled with the development of computer vision methods. Computed tomography (CT)‐based image analysis and Positron Emission Tomography (PET)‐based image analysis for the classification of malignant lymphomas have some disadvantages, including a lack of inter and intra‐observer variability. Thus, a robust deep learning‐aided malignant lymphoma classification model is implemented to identify the specific type of lymphoma. Initially, the input images are acquired from benchmark databases. The required images are processed via the proposed Hybrid Adaptive and Attentive Networks (HAAN) for the malignant lymphoma classification. Therefore, it is the combination of Dilated MobilenetV2 with Convolutional‐Recurrent Neural Network (RNN) for the specific cancer subtype classification process. The functionality of the suggested network is enhanced by tuning the parameters in the network via the Revised Iteration‐based Peregrine Falcon Optimization (RIPFO). Thus, the proposed model processes large volumes of input images quickly and accurately for obtaining efficient malignant lymphoma classification results. Finally, the performance of the developed framework is estimated with conventional methods. The analysis results prove that the accuracy of the malignant lymphoma subtype classification framework is higher than the baseline classification mechanisms. In order to prove the model effectiveness, the accuracy of the developed technique shows 93.67%, 94.74%, and 95.36% in terms of diverse activation functions like linear, sigmoid, and ReLU, respectively.

Background: Malignant lymphoma has gained popularity in various countries worldwide. Consequently, it is one of the most common malignancies of children in the Kurdistan region of Iraq. Objective: To find the correlation between sociodemographic data, clinical characteristics, risk group classification, and laboratory findings of pediatric patients with lymphoma, together with the correlation between survival rates and survival time among both types of lymphoma. Patients and methods: In this retrospective, cross-sectional, hospital-based study, the recorded data of 104 pediatric lymphoma patients (aged &lt;18 years) from Hiwa Haematology/Oncology Hospital and Shorsh Teaching Hospital, Sulaimaniyah, Iraq, were obtained from January 1, 2015, to January 1, 2025. A standard validated questionnaire was used to record the patient's sociodemographic data, including clinical data and laboratory findings. Then, the correlation between variables was determined. Results: The patients’ mean age was 12.00 ± 3.59 years, and their mean BMI was 17.20 ± 4.34 kg/m². The time from the onset of lymphoma to diagnosis ranged from 0 to 13 months. Most patients were males (70.2%), from low-income families (43.8%), living outside of the cities (65.4%), had NHL (53.8%) of stage II (28.6%), had no B symptoms (57.7%), received chemotherapy alone (55.8%), completed treatment (85.6%), and were alive (83.7%). Significant correlations were found between age group, BMI, lymphoma stage IV, lymphoma type/subtype, receipt of chemotherapy combined with radiotherapy, lactate dehydrogenase level, and survival rate of the patients. Additionally, HL patients had a longer survival rate and survival time (p≤0.05). Conclusions: NHL was more common and predominantly of high grade, linked to a lower survival rate and shorter survival time.

Hematological malignancies like leukemia and lymphoma are severe cancers with high relapse rates. Duvelisib (DUV) is a selective dual phosphatidylinositol 3-kinase-delta and gamma inhibitor with good potential for treating hematological malignancies. However, its application is subsided by poor solubility, permeability and side effects. Herein, we have designed a human serum albumin shell and liquid-lipid core type of nanocapsule system (DUV-NCs) for effective drug loading, enhanced circulation and improved anticancer potential of DUV. The DUV-NCs were extensively optimized with DoE, resulting in a mean particle size of 188.2 ± 1.1nm, PDI of 0.238 ± 0.018 and entrapment efficiency of 86.99 ± 1.40%. Moreover, a sustained release behaviour with around 80% release up to 48h was observed. DUV-NCs showed an IC50of (12.78 ± 0.66µg/mL), which was significantly decreased (P < 0.001) than the free drug (IC50: 26.08 ± 4.04µg/mL) in the MOLT-4 cell line. Qualitative and quantitative cellular uptake studies in MOLT-4 cells revealed considerably higher internalization of FITC-NCs than free FITC. DUV-NC-treated groups also displayed higher ROS generation, which was also evident from the increase in apoptotic bodies in MOLT-4 cells. Pharmacokinetic studies showed a 2.07-fold increase in MRT with a 3.56-fold rise in AUC0-t from DUV-NCs compared to free DUV. The DUV-NCs were found to be safe in toxicity studies with no major alterations in biomarkers compared to the control. In conclusion, DUV-NCs is a promising strategy to deliver DUV in hematological malignancies with improved efficacy and safety.

Protein-losing enteropathy (PLE) is a rare complication of systemic lupus erythematosus (SLE). A 38-year-old woman with well-controlled SLE developed abdominal pain, lower-extremity edema, anemia, and hypoalbuminemia. The patient was then diagnosed with PLE. Despite treatment with glucocorticoids and cyclophosphamide, persistent hypoalbuminemia was observed. A biopsy was performed using double-balloon enteroscopy due to small bowel lesions, which confirmed the diagnosis of diffuse large B-cell lymphoma. To the best of our knowledge, this is the first reported case of diffuse large B-cell lymphoma mimicking PLE associated with SLE. The possibility of malignant lymphoma should be considered in cases of treatment-resistant PLEs associated with SLE.

Recent studies show evidence of cognitive and psychosocial impairments and reduced quality of life (QoL) in adult survivors of childhood extracranial solid tumors and lymphomas, but limited research has addressed these issues in pediatric populations. The French RISK-N prospective study (2014-2021) evaluated 278 survivors of extracranial solid tumors or lymphomas (47% female, mean age at diagnosis and assessment: 6.2 and 11.7years). Patients with pre-existing neurological conditions were excluded. Sociodemographic, disease-related, and treatment data were collected. Cognitive performance was assessed using Wechsler Intelligence Scales for Children (WISC-IV, WISC-V). Psychosocial outcomes included parent and/or patient-reported executive functions (Behavior Rating Inventory of Executive Function), behavior (Conner's Parent Rating Scale), QoL (Pediatric Quality of Life Inventory), fatigue (Multidimensional Fatigue Scale), and depression (Children's Depression Inventory). Information on schooling and educational/rehabilitative interventions was also recorded. Diagnoses included lymphoma (25%), nephroblastoma (19%), neuroblastoma (19%), osteosarcoma (7%), other sarcomas (18%), and other tumors (12%). Mean Full Scale Intellectual Quotient [M(SD) = 99.44(15.62)] was as expected in the general population [M(SD) = 100(15)], but the WISC-IV Perceptual Reasoning Index was slightly lower [M(SD) = 95.4(15.0), <1.5 SD 14%]. Parent- and self-reports indicated greater executive dysfunction, inattention, fatigue, and reduced QoL. In multivariable regression models, poorer cognitive outcomes were associated with lower parental education and developmental/learning delays before diagnosis. Objective cognitive deficits were uncommon among pediatric cancer survivors, contrasting with a relatively high level of subjective cognitive and psychosocial complaints, highlighting the need for systematic screening and tailored clinical interventions.

Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL) is a rare aggressive T-cell lymphoma mostly found in Asia. It accounts for less than 5% of primary gastrointestinal malignant lymphomas, is rapidly progressing, and has a poor prognosis with a median survival of 7 months. The relatively small size of atypical cells coupled with brisk cryptitis can result in a misdiagnosis of lymphocytic proctocolitis. A strong index of suspicion is required to employ an appropriate IHC panel for this diagnosis. In this case report, we want to describe a 50-year-old patient who presented with chronic lower gastrointestinal symptoms and was diagnosed with MEITL involving the large intestine and ileum.

Disseminated mucormycosis is a fatal infection commonly observed in patients with prolonged neutropenia, such as those undergoing treatment for hematological malignancies or post-transplantation. This report describes a case of malignant lymphoma in a patient with no history of cytotoxic chemotherapy. The patient died early, and disseminated mucormycosis was identified during an autopsy. Notably, no imaging findings were suggestive of mucormycosis, which complicated the diagnosis. Given that both mucormycosis and malignant lymphoma were suspected from the initial presentation, it is important to consider mucormycosis as a potential differential diagnosis in patients with altered consciousness.

Collaboration between hematologists and primary care physicians (PCPs) is crucial for managing hematologic diseases, particularly malignancies. However, the specific challenges PCPs face in such coordination remain underexplored in Japan. The aim of this study was to investigate the difficulties and questions encountered by PCPs when providing care to patients with hematologic diseases and to identify potential barriers to effective collaboration with hematologists. We conducted a web-based, self-administered questionnaire survey among 4,207 physicians listed on the Japan Primary Care Association mailing list. Respondents with at least three years of clinical experience were eligible. The questionnaire covered demographics, involvement in home care, and challenges in referral and follow-up related to hematologic diseases. Quantitative data were analyzed using descriptive statistics; free-text responses were thematically analyzed using NVivo. A total of 90 PCPs responded. The most frequently referred conditions were malignant lymphoma, bone marrow failure, and myeloproliferative neoplasms. Common follow-up challenges included limited access to hematologists, role ambiguity, and inadequate communication. Thematic analysis revealed key difficulties: a shortage of specialists, complex treatment decisions for elderly patients, and psychological barriers in initiating consultations with hematologists. PCPs in Japan face both structural and psychological barriers when managing hematologic diseases, particularly in collaboration with hematologists. Enhancing bidirectional communication and addressing these barriers may improve continuity and quality of care.

The patient was a male in his 50s. He had been aware of headache since the end of April, X year, and was admitted to the Neurosurgery Department of X Hospital in early May; however, his headache and posterior neck pain worsened. He was discharged from the previous hospital and admitted to this hospital in late May. His consciousness was clear, and there were no abnormalities in his cranial nerves or limb motor systems. Tendon reflexes were normal and Babinski's sign was negative. He complained of posterior neck pain and remained in bed all day with his neck flexed backward. Head MRI showed a high fluid-attenuated inversion recovery (FLAIR) signal, high diffusion-weighted imaging (DWI) signal, and low T2* signal around the inferior horn of left lateral ventricle, and contrast-enhanced MRI showed a diffuse contrast effect on the cerebral surface, brainstem, and spinal cord soft membrane. Cerebrospinal fluid (CSF) analysis showed 98 cells/μl (66% mononuclear cells, 34% polymorphonuclear cells), protein level of 140 ‍mg/dl, and glucose level of 32 ‍mg/dl (simultaneous blood glucose 160 ‍mg/dl); cytology was negative. Malignant lymphoma, fungal/tuberculous meningitis, meningeal carcinomatosis, and granulomatous disease were suspected; however, no abnormalities were observed. In mid-June, the patient's condition suddenly deteriorated, and he died. Autopsy revealed an epithelioid glioblastoma (isocitrate dehydrogenase [IDH]-wild-type, World Health Organization [WHO] grade IV) near the left subventricular angle, with diffuse infiltration of the glioblastoma on the cerebral surface, brainstem, and spinal cord pia mater. The patient was diagnosed with glioblastoma with diffuse leptomeningeal spread.

The patient was a 46-year-old man with a family history of malignant lymphoma. He presented with bilateral submandibular and cervical lymphadenopathy, which resolved spontaneously. However, approximately one year later, he was admitted to our hospital for treatment of systemic lymph node swelling and bacterial pneumonia. Inguinal lymph node biopsy showed residual lymph follicles with T-zone expansion and numerous Epstein-Barr virus encoding region in situ hybridization (EBER-ISH) positive B-cells. Epstein-Barr virus (EBV) was also detected in the plasma, and EBV encephalitis was diagnosed. Following antibiotic treatment, the lymph node swelling regressed, and the patient was discharged. Based on the characteristic family history, susceptibility to infections, and EBV viremia, we suspected a primary immunodeficiency syndrome. XMEN disease caused by a pathogenic mutation in the magnesium transporter 1 (MAGT1) gene was diagnosed by genetic testing. To the best of our knowledge, no cases of XMEN disease from Japan have been reported in the literature. It is important to consider genetic testing when primary immunodeficiency is suspected.

Objective: This study aims to evaluate the clinical value of F-18 fluorodeoxyglucose (FDG) dual-time-point (DTP) PET/CT with semiquantitative analyses for predicting therapy response in patients with malignant lymphoma (ML). Materials and Methods: We evaluated 847 lesions in 39 patients diagnosed with ML, including Hodgkin Lymphoma (HL) and aggressive and indolent non-Hodgkin lymphoma (NHL). We calculated metabolic tumor volume (MTV), standardized uptake value (SUVmax), and total glycolytic activity (TGA) for each lesion during early (60 min) and delayed (120 min) scans, along with retention indices (RI). Interim PET/CT was then performed, and the performance of SUVmax and TGA cutoff values for assessing treatment response (Complete Response (CR) and Partial Response (PR)) was analyzed using ROC curve analysis and multivariate logistic regression. Results: In a study of 847 lesions, 817 CR lesions from 31 patients and 30 PR lesions from 8 patients were examined. The results showed that ΔSUVmax, ΔTGA, and the retention index in TGA (RI-TGA) were significantly higher in PR lesions compared to CR lesions, whereas no difference was observed for RI-SUVmax. The cut-off values established were ΔSUVmax &gt; 3.7, ΔTGA &gt; 14.94, and RI-TGA &gt; 26.85%, indicating a 3.5 times greater likelihood of PR. For patient-based assessments, change in whole-body TGA (ΔWB-TGA) with a cut-off of 181.98 was significant (sensitivity 100%, specificity 67.74%, PPV 44.4%, NPV 100%) Conclusions: ΔSUVmax, ΔTGA, and RI-TGA values may predict therapy response based on lesion evaluation, while only ΔWBTGA is a significant factor based on patient evaluation. Dual-time imaging and TGA assessment may help predict therapy responses and guide personalized treatment plans.