Primary Calvarial Lymphoma: A Case Report.

Calvarial lymphoma is radiologically similar in many respects to meningiomas, solid fibrous tumours, osteomyelitis, and metastatic carcinomas. Even though it is an extremely rare phenomenon, the initial suspicion and detection of calvarial lymphoma are paramount to establishing a correct diagnosis which helps to determine an appropriate management strategy. We present an illustrative rare case of primary calvarial lymphoma along with a literature review focusing on the best management strategy for this rare entity. A 45-year-old female presented to our center in March 2022. She had a history of forehead swelling, which was progressively increasing in size over time. The metastatic workup and bone marrow biopsy were negative. Initially, extensive surgery was planned to resect the lesion, but after a discussion with the multidisciplinary team, a biopsy of the lesion was taken, which revealed a large B-cell lymphoma. It is prudent to consider calvarial lymphoma in the differential diagnosis of a progressively growing skull lesion, which may obviate the need for large resective surgery. A biopsy plus chemoradiation may be all that is required.

Primary Cutaneous Diffuse Large B-cell Lymphoma Successfully Treated With R-CHOP Chemotherapy.

Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) represent approximately 10%-20% of primary cutaneous B-cell lymphomas. They present as nodules in the skin or as rapidly growing aggressive behavior tumors with a poor prognosis. In this article, we report a case of PCDLBCL presented with an aggressively enlarging skin lesion on the right cheek. This case was diagnosed based on clinicopathological features and characteristic immunohistochemical expression. During the 11-month follow-up period, the patient showed significant clinical improvement after undergoing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, abbreviated as R-CHOP chemotherapy, without evidence of extracutaneous dissemination or disease relapse.

Acute Pancreatitis Revealing a Diagnosis of Diffuse Large B-Cell Lymphoma.

Acute pancreatitis is a common gastroenterological condition that can occur due to several causes. While not required for diagnosis, imaging is often performed and may reveal unexpected findings such as pancreatic masses. Malignancies such as lymphoma are uncommon causes of acute pancreatitis, especially as the initial presentation of malignancy. We present a case of a young patient with acute pancreatitis caused by diffuse large B-cell lymphoma with extranodal disease secondarily involving the pancreas. Our case highlights the importance of keeping a broad differential for acute pancreatitis and considering rare etiologies such as pancreatic lymphoma in patients without another obvious culprit.

Diffuse large B-cell lymphoma with contemporary involvement of central and peripheral nervous system: A case report and literature review.

Introduction: Simultaneous involvement of the peripheral nervous system (PNS) and central nervous system (CNS) during the same period in diffuse large B-cell lymphoma (DLBCL) is rarely documented. In this particular case, the diagnosis of diffuse large B-cell lymphoma was pathologically confirmed, with invasion into the basal ganglia, diencephalon, and several peripheral nerves. The initial clinical manifestations were dyspnoea and hyperventilation. Case presentation: The patient presented to the hospital with fatigue, dyspnoea, and limb pain for over 7 months, accompanied by progressive breathlessness and unconsciousness in the last 6 days. Initial treatment with glucocorticoids for Guillain-Barre syndrome (GBS) proved ineffective in controlling the severe shortness of breath and hyperventilation, necessitating the use of ventilator-assisted ventilation. 18-Fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) showed that the basal ganglia, brainstem, and multiple peripheral nerves were thickened and metabolically active. There were atypical cells in the cerebrospinal fluid; the pathology indicated invasive B-cell lymphoma, demonstrating a propensity toward diffuse large B-cell lymphoma (DLBCL). After receiving chemotherapy, the patient regained consciousness and was successfully weaned off ventilator assistance but died of severe pneumonia. Discussion: The early clinical manifestations of DLBCL lack specificity, and multifocal DLBCL complicates the diagnostic process. When a single primary disease cannot explain multiple symptoms, the possibility of DLBCL should be considered, and nervous system invasion should be considered when nervous system symptoms are present. Once nervous system involvement occurs in DLBCL, whether the central or peripheral nervous system, it indicates a poor prognosis.

Prognostic effect of DNA methylation of BTG2 gene in Chinese hepatocellular carcinoma.

Background: This study aims to develop a prognostic model for overall survival based on potential methylation sites within B-cell translocation gene 2 (BTG2) in Chinese patients with hepatocellular carcinoma (HCC). Methods: This is a retrospective study. The beta values of nine CpG sites and RSEM normalized count values of BTG2 gene were extracted from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (TCGA-LIHC) dataset, with the beta value representing the methylation level by indicating the ratio of the intensity of the methylated bead type to the combined locus intensity. Pyrosequencing was performed to determine the range of methylation values surrounding cg01798157 site in BTG2 gene. A weighted linear model was developed to predict the overall survival (OS). Results: The beta value of cg01798157 was significantly negatively associated with the mRNA expression of BTG2 in the TCGA-LIHC dataset (Spearman's rho = -0.5306, P = 2.27 × 10-27). The methylation level of cg01798157 was significantly associated with OS in the cohort of 51 Chinese HCC patients (Hazard ratio = 0.597, 95% CI: 0.434-0.820, P = 0.001). Multivariate Cox regression analysis identified methylation level of cg01798157, cirrhosis, and microvascular invasion as independent prognostic factors. The prognostic efficiency of death risk score was superior to that of cirrhosis or microvascular invasion alone. Conclusions: The methylation level of cg01798157 in BTG2 may be an epigenetic biomarker in Chinese patients with resectable HCC.

Hospital healthcare resource utilization and costs for chimeric antigen T-cell therapy and autologous hematopoietic cell transplant in patients with large B-cell lymphoma in the United States.

The efficacy of chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is well-established. This study, using the Premier PINC AI Healthcare Database, assessed hospital costs and healthcare resource utilization (HRU) between CAR T-cell therapy and autologous hematopoietic cell transplant (AHCT) for 733 LBCL patients from 01/01/2017-04/30/2021 (166 CAR T and 567 AHCT from 37 US hospital systems. CAR T-cell therapy had higher index costs but lower non-pharmacy costs, shorter hospital stays, lower ICU utilization than AHCT. The CAR T-cell cohort also presented fewer preparatory costs and HRU. At a 180-day follow-up, AHCT had lower hospitalization rates and costs. Overall, despite higher index costs, CAR T-cell therapy has lower non-pharmacy costs and HRU during the index procedure and requires less preparation time with lower preparation HRUs and costs than AHCT. This has important implications for resource management and informed decision-making for stakeholders.

Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Cytogenetic and pathologic characterization of MYC-rearranged B-cell lymphomas in pediatric and young adult patients.

MYC-rearranged B-cell lymphoma (BCL) in the pediatric/young adult (YA) age group differs substantially in disease composition from adult cohorts. However, data regarding the partner genes, concurrent rearrangements, and ultimate diagnoses in these patients is scarce compared to that in adult cohorts. We aimed to characterize the spectrum of MYC-rearranged (MYC-R) mature, aggressive BCL in the pediatric/YA population. A retrospective study of morphologic, immunophenotypic, and fluorescence in situ hybridization (FISH) results of patients age ≤ 30 years with suspected Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL), and a MYC-R by FISH between 2013-2022 was performed. Two-hundred fifty-eight cases (129 (50%) pediatric (< 18 years) and 129 (50%) YA (18-30 years)) were included. Most MYC-R BCL in pediatric (89%) and YA (66%) cases were BL. While double-hit (DH) cytogenetics (MYC with BCL2 and/or BCL6-R, HGBCL-DH) was rare in the pediatric population (2/129, 2%), HGBCL-DH increased with age and was identified in 17/129 (13%) of YA cases. Most HGBCL-DH had MYC and BCL6-R, while BCL2-R were rare in both groups (3/258, 1%). MYC-R without an IG partner was more common in the YA group (14/116 (12%) vs 2/128 (2%), p = 0.001). The pediatric to YA transition is characterized by decreasing frequency in BL and increasing genetic heterogeneity of MYC-R BCL, with emergence of DH-BCL with MYC and BCL6-R. FISH to evaluate for BCL2 and BCL6 rearrangements is likely not warranted in the pediatric population but should continue to be applied in YA BCL.

Identification of B cell epitopes located on the surface in PB2 protein of H9N2 subtype avian influenza virus.

Avian influenza (AI) caused by H9N2 subtype avian influenza virus (AIV) poses a serious threat to poultry farming and public health due to the transmissibility and pathogenicity. The PB2 protein is a major component of the viral RNA polymerase complex (vRNP). It is of great significance for identifying the antigenic determinants of PB2 protein to explore the function of PB2 protein. In this study, PB2 sequence of H9N2 subtype AIV from 1090 to 1689 bp was cloned and expressed in the prokaryotic expression pET-28a vector. After purified, the recombinant PB2 protein with cutting gel was used to immunize BALB/c mice. After cell fusion, the Hybridoma cell lines secreting monoclonal antibodies (mAbs) targeting to PB2 protein were screened by indirect ELISA and Western blotting, and the antigenic epitopes of mAbs were identified by constructing truncated overlapping fragments in PB2 protein of H9N2 subtype AIV. The results showed that three hybridoma cell lines (4B7, 4D10, 5H1) that stably secreted mAbs special to PB2 protein were screened, and heavy chain of 4B7 was IgG2α, that of 4D10 and 5H1 were IgG1, in which three mAbs were Kappa light chain. Also, the minimum B-cell epitope recognized by 475LRGVRVSK482 and 528TITYSSPMMW537. Homology analysis showed that these two epitopes were conservative among the different subtypes of AIV strains and located on the surface of PB2 protein. The above findings provide an experimental foundation for further investigation of the function of PB2 protein and provide effective technical support for developing monoclonal antibody-based diagnostic kits.

Polymorphic lymphoproliferative disorder arising in a rheumatoid arthritis patient, presenting as fibrin-associated large B-cell lymphoma-like lesions in aortic and mitral valves.

We herein report a case of methotrexate-associated lymphoproliferative disorder (MTX-LPD) showing fibrin-associated large B-cell lymphoma-like heart valve lesions, and Epstein-Barr virus (EBV)-positive mucocutaneous ulcer-like cutaneous and oral mucosal lesions. MTX-LPD is a critical complication that can occur in RA patients who are treated with MTX. EBV also plays a defining or important role in LPDs. Among the sites of MTX-LPD, 40-50% occur in extranodal sites, including the gastrointestinal tract, skin, liver, lung, and kidney. There are few reports of MTX-LPDs involving the heart valves, and to the best of our knowledge, this is the first case to be reported in the English literature. The possibility of EBV-positive LPD should be considered in RA patients, even in patients with an atypical site, as in this case.

Prognostic model based on B cell marker genes for NSCLC patients under neoadjuvant immunotherapy by integrated analysis of single-cell and bulk RNA-sequencing data.

BACKGROUND: Neoadjuvant immunotherapy has evolved as an effective option to treat non-small cell lung cancer (NSCLC). B cells play essential roles in the immune system as well as cancer progression. However, the repertoire of B cells and its association with clinical outcomes remains unclear in NSCLC patients receiving neoadjuvant immunotherapy. METHODS: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data for LUAD samples were accessed from the TCGA and GEO databases. LUAD-related B cell marker genes were confirmed based on comprehensive analysis of scRNA-seq data. We then constructed the B cell marker gene signature (BCMGS) and validated it. In addition, we evaluated the association of BCGMS with tumor immune microenvironment (TIME) characteristics. Furthermore, we validated the efficacy of BCGMS in a cohort of NSCLC patients receiving neoadjuvant immunotherapy. RESULTS: A BCMGS was constructed based on the TCGA cohort and further validated in three independent GSE cohorts. In addition, the BCMGS was proven to be significantly associated with TIME characteristics. Moreover, a relatively higher risk score indicated poor clinical outcomes and a worse immune response among NSCLC patients receiving neoadjuvant immunotherapy. CONCLUSIONS: We constructed an 18-gene prognostic signature derived from B cell marker genes based on scRNA-seq data, which had the potential to predict the prognosis and immune response of NSCLC patients receiving neoadjuvant immunotherapy.

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.

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

INTRODUCTION: Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. METHODS: A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. RESULTS: In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. CONCLUSION: PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

Causal role of immune cells in psoriasis: a Mendelian randomization analysis.

Background: A growing body of evidence has shown that immune cells are linked to psoriasis. It is, however, still unclear if these associations reflect a relationship of cause and effect. Objective: We employed a two-sample Mendelian randomization (MR)-based study to elucidate the probable causative connection between immune cells and psoriasis. Methods: Summary information for psoriasis (Ncase = 5,427, Ncontrol = 479,171) was obtained from the European Bioinformatics Institute. Summarized statistical information on 731 immune cell features, including morphological parameters (MP; n = 32), relative cell number (n = 192), median fluorescence intensity (MFI) of surface antigens (n = 389), and absolute cell number (n = 118), was obtained from the genome-wide association studies (GWAS) catalog. The research consisted of forward MR analysis, in which immune cell traits were used as the exposure factor, and psoriasis was the outcome, as well as reverse MR analysis, in which psoriasis was used as the exposure factor, and immune cell traits were the outcome. We ran numerous sensitivity analyses to ascertain the study results for robustness, heterogeneity, and potential multiple-biological effects. Result: This research determined a probable causative connection between immune cells and psoriasis. In particular, we identified 36 distinct types of immune cells that are potentially causally linked to psoriasis. Conclusion: Our findings indicate strong causal correlations between 36 immunological phenotypes and psoriasis, thus, directing future clinical trials.

Co-Occurrence of Pityriasis Amiantacea and Cutis Verticis Gyrata Secondary to Leukaemia Cutis of the Scalp.

Introduction: Pityriasis amiantacea (PA) is a rare presentation characterized by the presence of extensive adherent scaling that tightly encircles and affixes tufts of hairs secondary to inflammatory or infectious dermatoses. However, the occurrence of PA as a consequence of leukaemia cutis has not been previously reported. Case Report: A 32-year-old man with B-cell acute lymphoblastic leukaemia (B-ALL) presented with severe scalp scaling and hair loss for 2 months. Examination revealed extensive, tightly adherent scales encircling and binding down hairs, along with haemorrhagic crusts. Skin examination showed nontender, partially blanchable papules forming ill-defined plaques, giving a cobblestone appearance. Trichoscopy revealed white crusts, tufting, and micro-haemorrhages. Scalp biopsy confirmed precursor B-ALL infiltration. He was diagnosed with PA with secondary cutis verticis gyrata due to leukaemia cutis and referred to a haemato-oncologist for further management. Discussion: Leukaemia cutis is a rare condition where leukaemia cells infiltrate the skin, often associated with acute myeloid leukaemia and ALL. It can lead to secondary verticis gyrata. The co-occurrence of PA and cutis verticis gyrata is rare and previously unreported, highlighting the need for increased awareness among clinicians.

BCD020 rituximab bioanalog compared to standard treatment in juvenile systemic lupus erythematosus: The data of 12 months case-control study.

BACKGROUND: Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. AIM: To compare the benefits of RTX above SOCT. METHODS: The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. RESULTS: Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. CONCLUSION: RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.

Advanced Practice Nursing and CAR-T Cell Therapy: Opportunities, Challenges and Future Directions.

OBJECTIVES: Chimeric antigen receptor (CAR)-T cell therapy is a new treatment for patients with myeloma and other B cell malignancies where advanced practice nurses (APN) can make a great contribution. The aim of this review is to identify key aspects of current literature relevant to APNs working with this population. METHODS: Discussion of selected peer-reviewed literature and best practice guidelines found through electronic database searches (CINAHL, MEDLINE). RESULTS: Although few APN roles in CAR-T cell therapy have been published to date, recent research suggests that the APN is central to the care of these patients. They are essential for continuity of care and navigation through the treatment process, providing an important and consistent point of contact for patients' and carers' anxieties and uncertainties. APNs play a central role in symptom management, as they constantly incorporate new experience and scientific findings into the refinement of existing protocols. The continuum of care extends far beyond the inpatient stay and addresses symptoms that may persist long after cytokine release syndrome and neurotoxicity have resolved. The APN may therefore make a relevant contribution to patients' health-related quality of life, given its likely correlation with the dynamics and intensity of treatment-related symptoms. The APN also takes on a leadership role in the treatment team. CONCLUSIONS: APNs use all core competencies to sustainably support and empower patients and caregivers. This is achieved through counseling and education, in addition to identifying, developing, and implementing evidence-based symptom management. They play pivotal roles in introducing new CAR-T cell products, educating teams, and advancing their role through APN networks. Finally, APNs are integral members of multiprofessional teams, supporting colleagues in ethically challenging patient situations. IMPLICATIONS FOR NURSING PRACTICE: APNs in the field of CAR-T cell therapy make an important contribution to the continuous care of patients, caregivers, and treatment teams.

Cost-effectiveness analysis 3L of axicabtagene ciloleucel vs tisagenlecleucel and lisocabtagene maraleucel in Japan.

Aim: Cost-effectiveness analysis (CEA) was performed to compare axicabtagene ciloleucel (axi-cel) with tisagenlecleucel (tisa-cel) and lisocabtagene (liso-cel) for treatment of relapsed or refractory large B-cell lymphoma in adult patients after ≥2 lines of therapy in Japan. Materials & methods: Cost-effectiveness analysis was conducted using the partition survival mixture cure model based on the ZUMA-1 trial and adjusted to the JULIET and TRANSCEND trials using matching-adjusted indirect comparisons. Results & conclusion: Axi-cel was associated with greater incremental life years (3.13 and 2.85) and incremental quality-adjusted life-years (2.65 and 2.24), thus generated lower incremental direct medical costs (-$976.29 [-¥137,657] and -$242.00 [-¥34,122]), compared with tisa-cel and liso-cel. Axi-cel was cost-effective option compared with tisa-cel and liso-cel from a Japanese payer's perspective.