Primary B-cell Research Articles

Surgical Intervention for Primary B-cell Lymphoma of the Spine: A Systematic Review and Meta-analysis of Clinical Presentation, Treatment, Postoperative Outcomes, and Histologic Markers.

Systematic review and meta-analysis. To perform a systematic review of the clinical symptoms, radiographic findings, and outcomes after spinal decompression in B-cell lymphoma. B-cell lymphoma is a potential cause of spinal cord compression that presents ambiguously with nonspecific symptoms and variable imaging findings. Surgical decompression is a mainstay for both diagnosis and management, especially in patients with acute neurological deficits; however, the efficacy of surgical intervention compared with nonoperative management is still unclear. The databases of Medline, PubMed, and the Cochrane Database of Systemic Reviews were queried for all articles reporting spinal B-cell lymphoma. Data on presenting symptoms, treatments, survival outcomes, and histologic markers were extracted. Using the R software "survival" package, we generated bivariate and multivariate Cox survival regression models and Kaplan-Meier curves. In total, 65 studies were included with 72 patients diagnosed with spinal B-cell lymphoma. The mean age was 56.22 (interquartile range: 45.00-70.25) with 68% of patients being males and 4.2% of patients being immunocompromised. Back pain was the most common symptom (74%), whereas B symptoms and cauda equina symptoms were present in 6% and 29%, respectively. The average duration of symptoms before presentation was 3.81 months (interquartile range: 0.45-3.25). The most common location was the thoracic spine (53%), with most lesions being hyperintense (28%) on T2 magnetic resonance imaging. Surgical resection was performed in 83% of patients. Symptoms improved in 91% of patients after surgery and in 80% of patients treated nonoperatively. For all 72 patients, the overall survival at 1 and 5 years was 85% (95% CI: 0.749-0.953; n = 72) and 66% (95% CI: 0.512-0.847; n = 72), respectively. Although surgery is usually offered in patients with acute spinal cord compression from B-cell lymphoma, chemotherapy and radiation alone offer a hopeful alternative to achieve symptomatic relief, particularly in patients who are unable to undergo surgery.

Development and validation of a survival nomogram in patients with primary testicular diffuse large B-cell lymphoma.

We developed and validated a nomogram for overall survival (OS) and cancer-specific survival (CSS) prediction in patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). Patients diagnosed with PT-DLBCL were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors were analyzed to establish a nomogram of OS and CSS. Patients were reclassified into high- and low-risk groups; survival was compared using Kaplan-Meier curves and log-rank tests. We collected 1099 PT-DLBCL cases (2000-2019) from SEER and randomized into training (n = 771) and validation (n = 328) cohorts. In univariate and multivariate Cox regression analyses, five prognostic indicators (age, treatment modality, diagnosis year, Ann Arbor stage, laterality) were used to establish a nomogram of OS and CSS. The nomogram demonstrated excellent discrimination and calibration, with concordance indices in the training and validation cohorts of 0.702 (95% confidence interval [CI], 0.677-0.727) and 0.705 (95% CI 0.67-0.74) for OS and 0.694 (95% CI 0.663-0.725) and 0.680 (95% CI 0.63-0.72) for CSS. The calibration curve and ROC analysis indicated good predictive capability of the nomogram. The constructed prognostic model showed good predictive value for PT-DLBCL to assist clinicians in developing individualized treatment strategies.

Primary Central Nervous System Lymphoma

Histopathologic classifications of primary central nervous system lymphoma(PCNSL)are covered by two WHO classifications; WHO classification of Tumors: Central Nervous System Tumours(WHO-CNS)and WHO classification of Tumors: Haematolymphoid Tumours(WHO-HAEM). The International Consensus Classification(ICC)is another recent comprehensive classification of hematolymphoid tumors that covers these disease entities. While these classifications mainly share the same principles for categorizing these tumors, there are several differences that should be noted owing to the nature of WHO-CNS(which covers only the lymphomas manifesting in the CNS, and the anatomic sites are described in the titles of some entities)and the introduction of new entities in the latest version(5th)of the WHO-HAEM(WHO-HAEM5). In the WHO-HAEM5, two novel entities related to the perception of PCNSLs are introduced: primary large B-cell lymphoma of immune-privileged sites and lymphomas arising in immune deficiency/dysregulation. These entities are largely based on the underlying biology shared by lymphomas that arise from different sites, including the central nervous system, and they combine and re-classify several types that had been defined separately according to their sites and etiologies in previous versions. Classifications of PCNSLs in future revisions of the WHO-CNS might be described as parts of these novel entities, and nomenclatures of some diagnostic entities may be subject to change accordingly. This review will mainly focus on the classification of lymphomas described in the 5th edition of WHO-CNS, along with its comparison with WHO-HAEM and ICC.

POSTER: IBCL-417 Primary Intracranial Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in Cerebral Localization: Case Report

POSTER: IBCL-417 Primary Intracranial Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in Cerebral Localization: Case Report

IBCL-417 Primary Intracranial Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in Cerebral Localization: Case Report

IBCL-417 Primary Intracranial Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in Cerebral Localization: Case Report

"Trident Sign" in Primary CNS B-Cell Spinal Cord Lymphoma.

"Trident Sign" in Primary CNS B-Cell Spinal Cord Lymphoma.

Primary central nervous system diffuse large B-cell lymphoma presenting as homonymous hemianopia

Post-transplant lymphoproliferative disorder rarely affects the central nervous system although it can have visually significant consequences depending on the location of intracranial involvement.

Impact of thiotepa dose-intensity in primary diffuse large B-cell lymphoma of the central nervous system undergoing autologous hematopoietic cell transplant with thiotepa/carmustine conditioning.

Thiotepa/carmustine (TT-BCNU) is a commonly used autologous transplant (ASCT) conditioning regimen for primary DLBCL of the CNS (PCNSL). The total thiotepa dose varies among TT-BCNU recipients, with some centers administering a total dose of 20 mg/kg, while others using 10 mg/kg. We retrospectively assessed the impact of thiotepa dose intensity on ASCT outcomes in 218 adult PCNSL patients who underwent a first ASCT with TT-BCNU conditioning and received either a total thiotepa dose of 10 mg/kg (TT-10 group; N = 90), or 20 mg/kg (TT-20 group; N = 128). The median follow-up of survivors was 22 months. The cumulative incidence of 1-year non-relapse mortality (NRM) for TT-10 and TT-20 cohorts were 6% (95%CI = 2-12%) vs. 4% (95%CI = 1-8%), respectively (p = 0.66). The 3-year cumulative incidence of relapse (15% vs. 13%; p = 0.67), progression-free survival (PFS) (71% vs. 80%; p = 0.25) and overall survival (OS) (79% vs. 83%; p = 0.56) were similar in the TT-10 and TT-20 groups, respectively. On multivariate analysis compared to TT-10, the TT-20 cohort was not associated with significantly different risk of NRM (Hazard ration [HR] = 0.77; p = 0.64), relapse/progression (HR = 0.87; p = 0.74), PFS (HR = 0.80; p = 0.48) or OS (HR = 1.10; p = 0.80). In conclusion thiotepa dose-intensity in TT-BCNU conditioning does not impact ASCT outcomes of PCNSL patients.

Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.

Emerging entities and molecular subgroups in large B-cell lymphomas (LBCLs) were discussed during the 2022 European Association for Haematopathology/Society for Hematopathology workshop in Florence, Italy. This session focused on newly recognized diseases and their diagnostic challenges. High-grade/large B-cell lymphoma with 11q aberration (HG/LBCL-11q) is defined by chromosome 11q-gains and telomeric loss. FISH analysis is recommended for the diagnosis. HG/LBCL-11q can occur in the setting of immunodeficiency, including ataxia-telangiectasia, and predominates in children. The morphological spectrum of these cases is broader than previously thought with often Burkitt-like morphology and coarse apoptotic bodies. It has a Burkitt-like immunophenotype (CD10+, BCL6+, BCL2-) but MYC expression is weak or negative, lacks MYC rearrangement, and is in contrast to Burkitt lymphoma 50% of the cases express LMO2. LBCL with IRF4 rearrangement (LBCL-IRF4) occurs mainly in the pediatric population but also in adults. LBCL-IRF4 has an excellent prognosis, with distinguishing molecular findings. IRF4 rearrangements, although characteristic of this entity, are not specific and can be found in association with other chromosomal translocations in other large B-cell lymphomas. Other molecular subgroups discussed included primary bone diffuse large B-cell lymphoma (PB-DLBCL), which has distinctive clinical presentation and molecular findings, and B-acute lymphoblastic leukemia (B-ALL) with IGH::MYC translocation recently segregated from Burkitt lymphoma with TdT expression. This latter disorder has molecular features of precursor B-cells, often tetrasomy 1q and recurrent NRAS and KRAS mutations. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed.

Intracranial hematolymphoid malignancies: A case series with molecular characterization

ObjectiveCentral nervous system (CNS) manifestations of hematologic malignancies are uncommon and often have a poor prognosis. As hematologic neoplasms are typically chemotherapy- and radiotherapy-sensitive, surgical resection is usually not indicated; thus, opportunities for in-depth characterization of CNS hematologic tumors are limited. Here, we report four cases of rare intracranial hematologic tumors requiring surgical intervention, allowing for histopathologic and genomic characterization. MethodsThe clinical course, genetic perturbations, and histopathological features are described for a case of 1) primary marginal zone B-cell lymphoma of the dura as well as cases of brain metastases of 2) cutaneous T-cell lymphoma, 3) acute myeloid leukemia/myeloid sarcoma, and 4) multiple myeloma. Targeted DNA sequencing, fluorescence in situ hybridization, cytogenetic analysis, flow cytometry and immunohistochemical staining were used to assess the lesions. ResultMolecular and histopathological characterizations of four unusual presentations of hematolymphoid diseases involving the CNS are presented. Genetic abnormalities were identified in each lesion, including chromosomal aberrations and single nucleotide variants resulting in missense or nonsense mutations in oncogenes. ConclusionsOur case series provides insight into unique pathological phenotypes of hematologic neoplasms with atypical CNS involvement. We offer targets for future studies by identifying potentially pathogenic genetic variants in these lesions, as the full implications of the novel molecular abnormalities described remain unclear.

Primary Diffuse Large B-Cell Lymphoma of the Rectum: A Case Report and Literature Review

Primary rectal lymphoma (PRL) is a rare form of gastrointestinal lymphoma, representing less than 0.5% of all colorectal neoplasms; Clinical symptoms are similar to those of rectal cancer. This article presents a rare case of primary rectal lymphoma discussed by a thorough review of the literature.

МЕТАБОЛИЧЕСКАЯ ОФЭКТ/КТ с 99mTc-1-Тио-D-ГЛЮКОЗОЙ В ДИАГНОСТИКЕ МЕТАСТАЗИРОВАНИЯ ДИФФУЗНОЙ-В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМЫ ПОЛОВЫХ ОРГАНОВ В ГОЛОВНОЙ МОЗГ (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

Purpose: To demonstrate a rare clinical case of early recurrence of verified primary genital lymphoma and the possibility of 99mTc-1-Thio-D-glucose (99mTc-TG) SPECT/CT using to brain metastasis diagnosis. Material and methods: A patient with a diagnosis of primary diffuse large B-cell genital lymphoma underwent magnetic resonance imaging (MRI) to assess the extent of the disease. Post-treatment follow-up included 18F-FDG PET/CT. To diagnose brain metastasis, 99mTc-TG SPECT/CT and MRI were performed. Results: A rare case of early recurrence of diffuse large B-cell lymphoma with a primary local lesion in the genital organs is described. The possibility of modern methods of nuclear medicine in the diagnosis of early recurrence of malignant lymphoma has been demonstrated. 99mTc-TG SPECT/CT and MRI, were useful for visualization of a high metabolic brain tumor at the outpatient stage and recommendation of high-dose therapy according to the scheme MT-R was done. Conclusion: The article presents a rare clinical case of early recurrence of diffuse large B-cell genital lymphoma. Possibilities of SPECT/CT with 99mTc-TG for visualization of lymphoma metastasis to the brain were demonstrated.

Unusually aggressive primary testicular diffuse large B-cell lymphoma initially presenting as systemic disseminating metastases in older adult men: a case report.

Herein, the authors describe the case of a 64-year-old man with the chief complaint of a painless unilateral scrotal mass. Computed tomography scans of the abdomen and a pelvic examination demonstrated a left testicular tumor with multiple lymphadenopathies partially aggregated in the para-aortic area and disseminated to multiple soft tissues and organs. Subsequently, the patient underwent a left radical orchiectomy. Pathological and immunohistochemical examinations confirmed the diagnosis of left PT-DLBCL with systemic disseminating metastases. PTL often aggressively spreads to other extranodal organs, such as the contralateral testis, central nervous system, lung, pleura, Waldeyer's ring, and soft tissues. In men over 60 years of age, PT-DLBCL is the most common testicular malignancy. However, extensive systemic metastasis as the initial presentation is extremely rare. PT-DLBCL has a dismal prognosis and requires radical orchiectomy followed by multimodal therapy and central nervous system prophylaxis or systemic intervention to improve survival. The diagnosis of PT-DLBCL through preoperative and imaging examinations is often challenging. Thus, histopathology and immunohistochemical markers play a crucial and valuable role in the definite diagnosis and differential diagnosis of PTLs.

Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6).

There is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard. The present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with MYC and BCL2 rearrangements (prDLBCL/HGBL-MYC/BCL2) (n = 13) and HGBL, not otherwise specified (NOS), with MYC and BCL6 rearrangements (prHGBL, NOS-MYC/BCL6) (n = 6) based on our previously published whole-exome sequencing (WES) cohort. For genomic analysis, the institutional MTB WES pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed and supplemented by a comprehensive immunohistochemical work-up. Consecutive database research and annotation according to established evidence levels for molecularly stratified therapies was performed (NCT-DKTK/ESCAT). Molecularly tailored treatment options with NCT-DKTK evidence level of at least m2A were identified in each case. We classified mutations in accordance with biomarker/treatment baskets and detected a heterogeneous spectrum of targetable alterations affecting immune evasion (IE; n = 30), B-cell targets (BCT; n = 26), DNA damage repair (DDR; n = 20), tyrosine kinases (TK; n = 13), cell cycle (CC; n = 7), PI3K-MTOR-AKT pathway (PAM; n = 2), RAF-MEK-ERK cascade (RME; n = 1), and others (OTH; n = 11). Our virtual MTB approach identified potential molecularly targeted treatment options alongside targetable genomic signatures for both prDLBCL/HGBL-MYC/BCL2 and prHGBL, NOS-MYC/BCL6. These results underline the potential of MTB consultations in difficult-to-treat lymphomas early in the treatment sequence.

Management of Primary Uterine Cervix B-Cell Lymphoma Stage IE and Fertility Sparing Outcome: A Systematic Review of the Literature.

The female genital tract can be involved as a secondary manifestation of disseminated lymphomas or leukaemia but can rarely be the primary site of so-called extranodal lymphomas. Primary lymphomas of the female genital tract can affect the uterine corpus, uterine cervix, vulva, vagina, or adnexa. Only about 0.008% of all cervical tumours are primary malignant lymphomas. The most common clinical presentation of primary cervical lymphomas is a history of prolonged minor abnormal uterine bleeding, while unstoppable bleeding at presentation is rarely reported in the literature. "B" symptoms related to nodal lymphomas are usually absent. Since vaginal bleeding is a nonspecific symptom, the first diagnostic hypothesis is usually of one of the more common female genital conditions such as cervical or endometrial carcinoma or sarcoma, fibroids, adenomyosis, or endometriosis. Cervical cytology is usually negative. Preoperative diagnosis requires deep cervical biopsy. No guidelines regarding optimal treatment exists; radiotherapy, chemotherapy, and surgery are used in different combinations. Conservative treatment with the combination of surgery and chemotherapy or surgery and radiotherapy has been reported in a few cases with apparent success. With this review, we aim to understand what the best therapeutic approaches for this rare pathology in young and elderly women are. Moreover, we find favorable pregnancy outcome in patients treated with a fertility sparing approach.

A Case of Primary Cardiac B-cell Lymphoma Diagnosed with Cardiac MRI

Primary cardiac tumors account for only 0.3% of all cardiac tumors; of these, lymphomas account for only 2% of all primary cardiac tumors. Cardiac lymphomas have a grim prognosis, often less than 1 year due to delays in diagnosis and treatment. Cardiac MRI is the gold standard for the imaging of cardiac tumors. We describe the case of a 76-year-old man with no significant past medical history who presented to the emergency department with a large pericardial effusion that was found to be consistent with cardiac lymphoma on cardiac MRI prior to tissue diagnosis of a primary cardiac diffuse large B-cell lymphoma. The clinical and radiological features of cardiac lymphoma are reviewed, and the therapeutic management and side-effects that the patient experienced are discussed.

Primary Splenic Diffuse Large B-Cell Lymphoma: A Case Report.

The differential diagnosis of splenic nodules or infiltrates is vast and challenging, and it includes haematological diseases, systemic infectious diseases but also non-malignant infiltrative diseases.Although some lymphomas frequently present with splenomegaly, this is not the case of DLBCL, with the exception of PS-DLBCL.PS-DLBCL is a very rare pathology, accounting for 1% of all DLBCL and less than 1% of all NHL.

Durable responses with ALK inhibitors for primary refractory anaplastic lymphoma Kinase-positive large B-cell lymphoma.

Durable responses with ALK inhibitors for primary refractory anaplastic lymphoma Kinase-positive large B-cell lymphoma.

Single-cell landscape of primary central nervous system diffuse large B-cell lymphoma

Understanding tumor heterogeneity and immune infiltrates within the tumor-immune microenvironment (TIME) is essential for the innovation of immunotherapies. Here, combining single-cell transcriptomics and chromatin accessibility sequencing, we profile the intratumor heterogeneity of malignant cells and immune properties of the TIME in primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) patients. We demonstrate diverse malignant programs related to tumor-promoting pathways, cell cycle and B-cell immune response. By integrating data from independent systemic DLBCL and follicular lymphoma cohorts, we reveal a prosurvival program with aberrantly elevated RNA splicing activity that is uniquely associated with PCNS DLBCL. Moreover, a plasmablast-like program that recurs across PCNS/activated B-cell DLBCL predicts a worse prognosis. In addition, clonally expanded CD8 T cells in PCNS DLBCL undergo a transition from a pre-exhaustion-like state to exhaustion, and exhibit higher exhaustion signature scores than systemic DLBCL. Thus, our study sheds light on potential reasons for the poor prognosis of PCNS DLBCL patients, which will facilitate the development of targeted therapy.

What factors are associated with the prognosis of primary testicular diffuse large B-cell lymphoma? A study based on the SEER database.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a relatively rare urological tumor with a high degree of malignancy and a poor prognosis. This study aimed to investigate the prognostic risk factors for survival of patients with PT-DLBCL, and then to construct a predictive model and verify its reliability. First, we selected subjects from the SEER database (2000-2018) and analyzed the survival of PT-DLBCL patients by Kaplan-Meier test. Then, we analyzed prognostic factors by Cox regression. Finally, the data from the training cohort were used to construct a prediction model and represented with a nomogram. We evaluated the nomogram using the consistency index (C-index), decision curve analysis (DCA), and the area under the subject operating characteristic curve (ROC). In addition, calibration curves were plotted to assess the agreement between the column plot model and the actual model. We identified five independent risk factors for patient prognosis affecting OS and CSS in patients with PT-DLBCL by univariate and multivariate analysis, including age, transversality, Ann Arbor staging, chemotherapy, and radiotherapy. According to the above factors, we constructed prognostic nomograms, and found that age contributed the most to the survival of patients with PT-DLBCL. The C-indexes for the nomogram of OS and CSS in the training cohort were 0.758 (0.716-0.799) and 0.763 (0.714-0.812), and in the validation cohort were OS and CSS 0.756 (0.697-0.815) and 0.748 (0.679-0.817). We produced the first nomogram of PT-DLBCL, and it can be used to evaluate the CSS and OS of patients to determine the prognosis of patients.