Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy decreases lean body mass and appendicular skeletal muscle mass index even until one year after the final treatment in patients with B-cell non-Hodgkin lymphoma.

Sarcopenia is an independent prognostic factor for several solid cancers, including B-cell non-Hodgkin lymphoma (B-NHL). However, previous reports have measured the parameters of loss of skeletal muscle as sarcopenia only once before chemotherapy and have predicted poor outcomes. In this study, changes in body composition were measured in patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy for B-NHL using the InBody 720 analyzer throughout the therapy. Twenty-seven patients who achieved complete remission and survived for one year after the last cycle were included in the study. Body composition was evaluated immediately before initiation and fourth cycle, and one month and one year after the last cycle. Throughout the follow-up period, the lean body mass index (LBMI) and appendicular skeletal muscle mass index (ASMI) showed significant transient decreases even one year following the last cycle (p < 0.001, p = 0.002, respectively). Body fat index (BFI) and body fat percentage (BF%) decreased until one month after the last cycle; however, they reached levels higher than the baseline levels, +22.1% and +15.9%, respectively, at 1 year from the last cycle. The loss of skeletal muscle mass did not recover even one year after the last cycle. Interventions in nutritional management are needed to prevent sarcopenia in patients treated with R-CHOP therapy.

Laparoscopic Partial Splenectomy May Be Valuable for the Diagnosis of Malignant Lymphoma: A Case Report.

Background/Aim: Diagnosing primary splenic malignant lymphoma (PSML) is challenging due to the non-specific nature of splenomegaly, necessitating splenic biopsy for confirmation. However, performing partial splenic resection for diagnostic purposes is an elective procedure due to the risk of major hemorrhage. Despite the longstanding practice of splenectomy over the past few decades, it remains invasive and may result in severe early or late complications. Hence, we present laparoscopic partial splenectomy (LPS) in a patient suspicious of PSML for diagnostic purposes in this study. Case Report: An 81-year-old woman presented to our hospital with a one-month history of fever and dry cough. Atypical cells had been detected in her peripheral blood nine months ago. However, at that time, a bone marrow examination did not reveal any atypical cells. The laboratory tests revealed a soluble interleukin receptor-2 levels of 4,667 U/dl and atypical cells were also found in peripheral blood. Abdominal computed tomography showed splenomegaly without any other relevant findings. These findings are suspicious of PSML and LPS without vessel ligation was performed and a small fraction of the spleen from the inferior pole measuring 1.8×1.0 cm was resected. The operation lasted for 63 min with minimal estimated blood loss. Histopathological findings were compatible with the diagnosis of diffuse B-cell lymphoma. The postoperative clinical course was uneventful, and splenomegaly demonstrated improvement six months after the operation. Conclusion: LPS without vessel ligation for biopsy may be valuable for the diagnosis of malignant lymphoma, particularly when there are no swollen lymph nodes, as it offers a less invasive approach.

Inflammatory Back Pain and Psoriasis: Expecting Spondyloarthritis, Discovering Lymphoma.

Inflammatory back pain is a characteristic of spondyloarthritis. It is not, however, an exclusive symptom of inflammatory rheumatic diseases as it can also be associated with non-inflammatory entities. Infrequently, the etiology can be found in neoplastic conditions such as malignant lymphoma. Even in the presence of comorbidities indicatory of underlying rheumatic disease, like psoriasis vulgaris, the clinician should not be led astray. It is essential to pay attention to contradictory findings, as treatment crucially differs depending on diagnosis. Herein, we report on a psoriasis patient who presented with characteristic inflammatory back pain and deceptive imaging results. While the patient was initially thought to suffer from an inflammatory rheumatic disease with axial involvement, it was the accompanying atypical circumstances, particularly her age, that instantly challenged the diagnosis of axial psoriatic arthritis. She was eventually diagnosed with stage IV follicular lymphoma that manifested with rare and exclusively extranodal lesions and spondyloarthritis-like morphology. This case effectively demonstrates the importance of a thorough diagnostic workup and how certain clinical factors, such as the patient's age, should be considered when confronted with inflammatory back pain.

Ultrasonographic diagnosis of cervical lymph nodes.

Many patients visit outpatient clinics suffering from cervical lymphadenopathy. For those patients, ultrasonography is useful in differentiating inflammatory diseases and malignant tumors. On ultrasonographic images, normal lymph nodes are indicated as hypoechogenic masses with a well-defined border. The medullary portion near the lymph node hilum is hyperechogenic, so-called fatty hilum (FH). Color Doppler imaging reveals that blood flows from the lymph node hilum to FH. In lymph node metastasis, a metastatic focus grows within lymph nodes, which displaces and destroys the structure of normal lymph nodes. Ultrasonography can be used to detect FH, disappearance and unevenness of blood flow within lymph nodes, cyst formation, and so on. It is important to closely observe the inside of lymph nodes and make a diagnosis via ultrasonography, based on the criteria for diagnosing lymph node metastasis from head and neck squamous cell carcinoma. Additionally, it is also necessary to distinguish among inflammatory lymphadenopathy and malignant lymphoma.

Serum Soluble IL-2 Receptors Are Elevated in Febrile Illnesses and Useful for Differentiating Clinically Similar Malignant Lymphomas from Kikuchi Disease: A Cross-Sectional Study.

Background: The use of serum soluble interleukin 2 receptor (sIL-2R) for the diagnosis of febrile illnesses has not been examined. In this study, febrile patients were classified according to etiology and disease, and serum sIL-2R levels were evaluated. We determined whether serum sIL-2R is a useful marker for differentiating between malignant lymphoma (ML) and non-ML patients and between patients with ML and Kikuchi disease, which present similar clinical manifestations. Methods: This study was a cross-sectional study and included 344 patients with uncomplicated hemophagocytic syndrome, who had a fever of 38 °C or higher within 1 week of admission to our institution. Patient serum sIL-2R was measured, and the serum sIL-2R values are shown as median and IQR. Results: Serum sIL-2R increased above the upper reference limit in all disease groups with fever. The serum sIL-2R level in ML patients (n = 13) was 4760 (2120-6730) U/mL and significantly higher (p < 0.001) than the level of 998 (640-1625) U/mL in non-ML patients (n = 331). The serum sIL-2R level in ML patients (n = 13) was also significantly higher (p < 0.001) compared with that in patients with Kikuchi disease (n = 20; 705 (538-1091) U/mL). Conclusions: Serum sIL-2R tends to exceed the upper reference limit in patients with febrile illnesses. We conclude that the measurement of serum sIL-2R is useful for differentiating ML from non-ML and ML from Kikuchi disease.

Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma.

The goal of the study involved the comparison of clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of malignant lymphoma (ML). The effectiveness of allo-HSCT versus auto-HSCT in the treatment of ML was compared by searching EMBASE, PubMed, Web of Science, and the Cochrane Library for relevant studies. The confidence intervals (CI) and odds ratio (OR) of the article's outcomes were described by a forest plot. Finally, 972 patients in seven articles were included. Overall survival (OS) did not differ significantly between allo-HSCT and auto-HSCT groups (OR = 0.87, 95% CI: 0.66-1.14, P = 0.31). Furthermore, there was no significant difference in adverse reactions (AR) between the two groups (OR = 1.35, 95% CI: 0.81-2.24, P = 0.25). We observed a significant difference in progression-free survival (PFS) between the two groups (OR = 4.14, 95% CI: 2.93-5.35, P < 0.01). There was no evidence of publication bias in this meta-analysis. The incidence of OS and AR differ significantly between allo-HSCT and auto-HSCT, but the PFS was longer in ML patients who received allo-HSCT.

Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

A study of criteria for grading follicular lymphoma using a cell type classifier from pathology images based on complementary-label learning.

We propose a criterion for grading follicular lymphoma that is consistent with the intuitive evaluation, which is conducted by experienced pathologists. A criterion for grading follicular lymphoma is defined by the World Health Organization (WHO) based on the number of centroblasts and centrocytes within the field of view. However, the WHO criterion is not often used in clinical practice because it is impractical for pathologists to visually identify the cell type of each cell and count the number of centroblasts and centrocytes. Hence, based on the widespread use of digital pathology, we make it practical to identify and count the cell type by using image processing and then construct a criterion for grading based on the number of cells. Here, the problem is that labeling the cell type is not easy even for experienced pathologists. To alleviate this problem, we build a new dataset for cell type classification, which contains the pathologists' confusion records during labeling, and we construct the cell type classifier using complementary-label learning from this dataset. Then we propose a criterion based on the composition ratio of cell types that is consistent with the pathologists' grading. Our experiments demonstrate that the classifier can accurately identify cell types and the proposed criterion is more consistent with the pathologists' grading than the current WHO criterion.

A pediatric case of Burkitt's lymphoma with bile duct obstruction requiring surgical biliary reconstruction.

BACKGROUND: Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt's lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery. CASE PRESENTATION: A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed. CONCLUSIONS: Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue.

Neurolymphomatosis diagnosed after a recurrence of facial palsy.

Neurolymphomatosis (NL) is a rare complication of non-Hodgkin's lymphoma, characterized by the infiltration of lymphoma cells into the peripheral nerves. A 54-year-old woman initially presented with right facial palsy without any other significant symptoms and was diagnosed with Bell's palsy. Despite initial improvement, her condition recurred, prompting further evaluation. Magnetic resonance imaging (MRI) revealed contrast enhancement from the tympanic segment to the surface of the masseter muscle along the right facial nerve and an adjacent mass lesion. Biopsy of the mass revealed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma. Chemotherapy resulted in complete resolution of facial palsy. Follow-up MRI confirmed the absence of contrast enhancement along the facial nerve. Facial palsy was considered to be caused by NL. This case was classified as that of primary NL because the facial palsy was the first manifestation of a hematologic malignancy. Recurrent facial palsy, which is atypical in Bell's palsy, led to further evaluation with MRI, which finally resulted in the diagnosis of malignant lymphoma. In cases of recurrent facial palsy, clinicians should consider various diagnoses, including that of NL, and advocate early imaging tests and biopsy, if possible, for accurate diagnosis and improved outcomes.

[Primary central nervous system lymphoma presenting as a unilateral internal auditory canal lesion: a case report].

A 61-year-old man with right hearing loss and staggering for seven months was diagnosed with sudden deafness although previous evaluation with MRI indicated minor abnormal findings. During follow-up, he developed hypogeusia, right facial nerve palsy, pain in right mandible, right-sided temporal pain, and cerebellar ataxia. Cerebrospinal fluid examination at admission revealed reduced glucose concentration and elevated soluble interleukin-2 receptor (sIL-2R) level, whereas serum sIL-2R level was within the normal range. Brain MRI showed a swollen contrast-enhanced lesion extending from the right internal auditory canal to the middle cerebellar peduncle. Gallium-67 (67Ga) single-photon emission-computed tomography-computed tomography (SPECT-CT) revealed abnormal accumulation at the lesion site. Pathologic analysis of the tumor after resection led to the diagnosis of primary central nervous system lymphoma. In the present case, the MRI and 67Ga SPECT-CT characteristics were distinct from those of vestibular schwannoma. In addition, elevation of sIL-2R in the cerebrospinal fluid but not in serum was useful for differential diagnosis.

Optimizing random skin biopsies: a review of techniques and indications for intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of malignant lymphoma, is diagnosed by observation of intravascular proliferation of tumor cells in samples taken from affected organs. However, diagnosis of IVLBCL is usually difficult due to the lack of mass formation. IVLBCL may be fatal when the diagnosis is delayed, so an accurate early diagnosis is the key to successful treatment. Random skin biopsy (RSB), in which specimens are sampled from normal-appearing skin, has been reported as useful. However, the specific method of RSB remains controversial, with individual institutions using either the punch method or the incisional method. Research has shown that the incisional method has higher sensitivity than the punch method. We discuss whether this difference might owe to the collection of punch specimens from an insufficient depth and whether the punch method might result in false negatives. For RSB, we recommend taking specimens not only from normal-appearing skin, but also from any lesional skin, because lesions may reflect micro IVLBCL lesions. To ensure accurate diagnosis, both dermatologists and hematologists should know the proper method of RSB. This review summarizes the appropriate biopsy method and sites for RSB.

A rare case of primary cardiac diffuse large B-cell lymphoma imaged with 18F-FDG PET/CT: a case report and literature review.

Background: One of the exceptionally rare forms of non-Hodgkin's lymphoma (NHL) is primary cardiac lymphoma (PCL). The principal clinical manifestation in patients with PCL involves cardiac symptoms resulting from myocardial infiltration by lymphoma, including arrhythmias, heart failure, and chest pain. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for assessing clinically staging NHL. Case report: We present a rare case involving a 72-year-old woman diagnosed with primary intracardiac diffuse large B-cell lymphoma. For further staging, the patient underwent 18F-FDG PET/CT, revealing multiple nodular soft tissue density lesions in the heart and pericardium exhibiting increased FDG metabolism (SUVmax = 12.1). The supradiaphragmatic and infradiaphragmatic segments of the inferior vena cava exhibited irregular morphology with localized nodular changes and increased FDG metabolism in the surrounding area (SUVmax = 9.7). Additionally, multiple enlarged lymph nodes were identified in the left axilla, mediastinum, and adjacent to the abdominal aorta, displaying heterogeneous FDG uptake with an SUVmax of 9.3, indicating lymphoma involvement. The above imaging findings suggested that the mass was a PCL. Hence, the patient underwent a combination of chemotherapy and immunotherapy using R-CDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone). Following two courses of treatment within a span of 2 months, there was a partial remission observed in the cardiac lymphoma and the enlarged lymph nodes. Conclusion: The case elucidated in this report contributes to an enhanced understanding of the disease for clinicians, with 18F-FDG PET/CT providing comprehensive insights into the extent of cardiac involvement, as well as the engagement of extracardiac organs and pathologic lymph nodes. The 18F-FDG PET/CT examination not only visually delineates the lesion's location and extent but also serves as a cornerstone for clinical tumor staging, offering valuable support for treatment monitoring and subsequent follow-up.

Hepatic Tumor Rupture in Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders of the B-cell Type in a Patient With Chronic Rheumatoid Arthritis.

A 75-year-old woman on tumor necrosis factor inhibitors for rheumatoid arthritis presented with hematemesis and a gastric biopsy revealed diffuse large B-cell lymphoma with possible bulky left liver tumor involvement. On the second day of treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the patient experienced abdominal pain followed by shock vitals. A contrast-enhanced computed tomography scan revealed a ruptured liver. Transcatheter arterial embolization (TAE) was performed to stop the bleeding. This is the first case of hepatic tumor rupture secondary to an iatrogenic immunodeficiency-associated lymphoproliferative disorder of the B-cell type that was successfully treated with TAE to achieve hemostasis.

Treatment of Catheter-Associated Internal Jugular Vein Thrombosis Using Apixaban for Less Than Three Months in Two Patients With Aggressive B-cell Lymphoma Undergoing Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone Therapy.

The selection of anticoagulant therapy and appropriate duration of treatment for central venous (CV) catheter-associated internal jugular vein thrombosis in patients with malignant lymphoma remain unclear. Two cases of aggressive B-cell lymphomas treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), in which apixaban administered for less than three months was effective against CV catheter-associated internal jugular vein thrombosis, are reported. In one case, the right internal jugular vein thrombosis developed after eight courses of R-CHOP; when apixaban was orally administered for 37 days after the CV catheter was removed, the thrombus completely dissolved and did not recur for 27 months. In the other case, right internal jugular vein thrombosis developed after four courses of R-CHOP; two additional courses of the R-CHOP were administered alongside oral apixaban administration without catheter removal. After 66 days of oral apixaban, the thrombus completely dissolved, the CV catheter was removed, and no recurrence was observed for 8.5 months.

Pre-treatment systemic inflammation response index and systemic immune inflammation in patients with primary central nerve system lymphoma as a useful prognostic indicator.

PURPOSE: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) are based on neutrophil, monocyte, platelet, and lymphocyte counts. The SIRI and SII are used to predict the survival of patients with malignant tumors. It is well known that the inflammatory immune response is closely related to cancer occurrence and progression. In the present study, we evaluated the potential prognostic significance of SIRI and SII in patients with primary central nervous system lymphoma (PCNSL). METHODS: Fifty-eight consecutive patients were enrolled in this study between November 2006 and May 2022. Among the 58 patients, 47 patients with sufficient blood test data and follow-up were analyzed. The patients with steroid intake at the time point of the blood test and higher C-reactive protein were excluded. RESULTS: The median follow-up and survival times were 31 and 36 months, respectively. The optimal cutoff SIRI value was based on the receiver operating characteristic curve (ROC) for overall survival (OS) and stratified patients into low (< 1.43 × 109/L, n = 22) and high (≥ 1.43 × 109/L, n = 25) SIRI groups. The optimal cutoff SII value based on the ROC for OS stratified patients into low (< 694.9, n = 28) and high (≥ 694.9, n = 19) SII groups. A low SIRI value was associated with longer OS (p = 0.006). Furthermore, a low SII value was associated with longer OS (p = 0.044). The prognostic factors associated with prolonged survival in univariate analysis using the Cox proportional hazard model were age < 65 years, low SIRI, and low SII. The multivariate analysis demonstrated that age < 65 years and low SIRI independently predicted longer OS. CONCLUSION: Simple, less expensive, and routinely ordered preoperative blood count assessments such as SIRI and SII predict the OS of patients with PCNSL. This study demonstrated that PCNSL is associated with pre-treatment systemic immune-inflammation states.

PrecisionLymphoNet: Advancing Malignant Lymphoma Diagnosis via Ensemble Transfer Learning with CNNs.

Malignant lymphoma, which impacts the lymphatic system, presents diverse challenges in accurate diagnosis due to its varied subtypes-chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Lymphoma is a form of cancer that begins in the lymphatic system, impacting lymphocytes, which are a specific type of white blood cell. This research addresses these challenges by proposing ensemble and non-ensemble transfer learning models employing pre-trained weights from VGG16, VGG19, DenseNet201, InceptionV3, and Xception. For the ensemble technique, this paper adopts a stack-based ensemble approach. It is a two-level classification approach and best suited for accuracy improvement. Testing on a multiclass dataset of CLL, FL, and MCL reveals exceptional diagnostic accuracy, with DenseNet201, InceptionV3, and Xception exceeding 90% accuracy. The proposed ensemble model, leveraging InceptionV3 and Xception, achieves an outstanding 99% accuracy over 300 epochs, surpassing previous prediction methods. This study demonstrates the feasibility and efficiency of the proposed approach, showcasing its potential in real-world medical applications for precise lymphoma diagnosis.

B-cell Follicular Lymphoid Hyperplasia (Pseudolymphoma) of the Oral Cavity: A Diagnostic Quandary.

Pseudolymphoma is a reactive process involving lymphadenopathy, polyclonal proliferation of B or T-cells, simulating oral lymphoma. With its incidence being very rare, only four cases have been reported in oral cavity with the detailed immunocytochemical examination, which can be due to this entity's unawareness, underdiagnosis or overdiagnosis. It is prerogative to perform immunocytochemical investigations to prevent overdiagnosis as lymphoma, which can be debilitating to the patient. Wherein the treatment of pseudolymphoma initially includes topical or intralesional corticosteroid, antibiotics to surgical and radiotherapy based on its etiology. Herein, we discuss B-cell follicular lymphoid hyperplasia previously diagnosed as small round cell tumor.