Primary B-cell Research Articles

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.

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.

Outcomes of stereotactic radiosurgery in central nervous system lymphoma: A single institution experience.

e14061 Background: Primary or systemic high-grade B-cell lymphoma with secondary central nervous system lymphoma (PCNSL or SCNSL) are currently treated with high-dose methotrexate (HD-MTx) based chemo-immunotherapy regimens with/without whole brain radiation therapy (WBRT). CNS relapse can occur in up to 50% of patients with PCNSL or SCNSL. WBRT has been used as a salvage therapy for those patients. However, long-term neurological toxicities significantly reduce its clinical benefit. Stereotactic radiosurgery (SRS) is the administration of a localized, high dose of ionizing radiation. Limited studies exist exploring SRS as a treatment modality in relapsed/refractory (r/r) PCNSL/SCNSL. Methods: We conducted a retrospective single-center study evaluating the clinical efficacy of SRS in r/r PCNSL/SCNSL. Demographic, clinical, pathological, and treatment characteristics were collected in 29 r/r PCNSL (N=17)/SCNSL (N=12) patients, age ≥ 18 years, who received SRS between 01/2000 and 01/2023. Progression-free survival (PFS) and overall survival (OS) were calculated and reported using Kaplan-Meier analyses and log-rank tests. Results: Baseline characteristics are summarized (Table). The median Karnofsky performance status and Charlson comorbidity index were 70 and 5 respectively. For patients with PCNSL (N=17), the most common prior chemotherapy regimen administered was rituximab (R) in combination with the DeAngelis regimen (N=12), followed by the MATRIX regimen (N=3). In patients with SCNSL, the most common systemic chemotherapy regimen used was R + CHOP (N=9). Few patients received temozolomide (N=2). 5/29 (17%) of patients received WBRT before SRS. The overall response rate (ORR) to SRS in r/r PCNSL was 60% (7 CR and 2 PR). The ORR in r/r SCNSL was 83% (7 CR and 3 PR). The median OS of the overall cohort was 7.0 months (95% CI 5.1-8.9), while the median PFS was 5.0 months (95% CI 1.2-8.7). For patients with PCNSL, the median OS was 10.0 months (95% CI 2.2-17.7), and only 7 months (95% CI 1.8-12.1) for patients with SCNSL. Prior WBRT was associated with worse survival outcomes. Of interest, WBRT was avoided in 24/24 patients (100%). Conclusions: Our data support that CNSL patients can benefit from SRS therapy, with acceptable OS and PFS. In addition, the disease control spared patients from WBRT and therefore, mitigated neurological complications associated with that modality. [Table: see text]

IDENTIFICATION OF GENOMIC BIOMARKERS OF DISEASE PROGRESSION AND SURVIVAL IN NEWLY‐DIAGNOSED PRIMARY CNS LYMPHOMA

Introduction: There is a significant unmet need for robust genomic biomarkers that identify patients with newly-diagnosed primary CNS lymphoma (PCNSL) at high risk of progression, both during standard methotrexate-based induction as well as after dose-intensive consolidation. Methods: We performed targeted next-generation sequencing of 529 cancer genes of formalin-fixed, paraffin-embedded tumors from 74 patients with newly diagnosed primary CNS diffuse large B-cell lymphoma using the UCSF500 Cancer Panel and the Institute for Human Genetics CLIA Laboratory. The assay detects structural variants including single nucleotide variants, small insertions and deletions, and copy-number alterations (CNAs). Sixty-four EBV-negative PCNSL patients treated with a standard methotrexate, temozolomide, rituximab (MTR) induction were available for complete analysis. Results: We identified frequent mutations involving MYD88 (77%), CD79B (41.9%), ETV6 (27%) and BTG1 (25.7%) as well as frequent CNA involving 6q loss (62.5%), 9p loss (34.4%) and 12 gain (31.3%). Three genomic alterations were most significantly associated with early disease progression in PCNSL: (1) Alterations at 6p21.3, predominantly copy neutral loss of heterozygosity (CN-LOH) at the HLA Class I (HLA-A, B, C) and Class II loci (HLA-DR, DP, DQ, TAP1) as well as homozygous deletion of HLA Class II; (2) Mutations of tumor suppressor genes BTG1 and ETV6. Overall, these genomic alterations were detected in 28 out of 31 progression events in the cohort. The subgroup with either CN-LOH or homozygous deletion at 6p had the earliest progression, followed by the subgroup with mutations at either BTG1/ETV6 and no 6p CN-LOH or homozygous deletion, compared to no alterations at these 3 loci. 10 of 18 tumors with these alterations at 6p also contained BTG1 and/or ETV6 mutations. Survival analysis demonstrates that the subgroup with 6p CN-LOH or homozygous deletion had the earliest progression, followed by the subgroup with BTG1/ETV6 mutations compared to no alterations at these 3 loci (PFS p = 3.7e-5, OS p = 0.0017, logrank test, Figure 1). Multivariate Cox proportional hazard analysis demonstrated a significant 3.24-fold increased risk of progression with 6p CN-LOH/homozygous deletion or BTG1/ETV6 mutations (p = 3.5e-5, adjusted by Age, KPS, IELSG, MSKCC, IOL, Maintenance, and Consolidation). The research was funded by: National Cancer Institute NIH R01CA139-83-01A1 Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, genomics, epigenomics, and other-omics No conflicts of interests pertinent to the abstract.

Autologous Hematopoietic Stem Cell Transplantation is an Effective Treatment Option in Early Relapsed and Primary Refractory Diffuse Large B-Cell Lymphoma.

Introduction: 10-15% of diffuse large B-cell lymphomas (DLBCL) patients fail to achieve complete response (CR) after R-CHOP, and are considered primary refractory. There is limited transplant data in this population.
 Objetive: to evaluate the outcomes of primary refractory DLBCL patients transplanted at our center.
 Results: we evaluated 34 R/R patients treated with R-CHOP as first line. After second line, 30.4% of primary refractory/early relapse achieved CR, and 88.2% did so after ASCT. Median follow-up: 56.1 months, median OS was not reached; the estimated 5-year OS was 61.7%. Median OS of late relapse (Group 1) was not reached, and was 52 months for primary refractory/early relapse (Group 2) (p=0.023). The 5-year OS was 87.5% in Group 1 vs 49% in Group 2 (p=0.023).
 Conclusions: Primary refractory and early relapsed DLBCL undergoing second-line therapy and ASCT have worse OS compared to late relapse. However, 49% of primary refractory patients who proceeded to ASCT had prolonged survival, which supports the role of ASCT in this population.

Preclinical Evidence of an Allogeneic Dual CD20xCD22 CAR to Target a Broad Spectrum of Patients with B-cell Malignancies.

Despite the remarkable success of autologous chimeric antigen receptor (CAR) T cells, some patients relapse due to tumor antigen escape and low or uneven antigen expression, among other mechanisms. Therapeutic options after relapse are limited, emphasizing the need to optimize current approaches. In addition, there is a need to develop allogeneic "off-the-shelf" therapies from healthy donors that are readily available at the time of treatment decision and can overcome limitations of current autologous approaches. To address both challenges simultaneously, we generated a CD20xCD22 dual allogeneic CAR T cell. Herein, we demonstrate that allogeneic CD20x22 CAR T cells display robust, sustained and dose-dependent activity in vitro and in vivo, while efficiently targeting primary B-cell non-Hodgkin lymphoma (B-NHL) samples with heterogeneous levels of CD22 and CD20. Altogether, we provide preclinical proof-of-concept data for an allogeneic dual CAR T cell to overcome current mechanisms of resistance to CAR T-cell therapies in B-NHL, while providing a potential alternative to CD19 targeting.

Relapse of Ocular Lymphoma following Primary Testicular Diffuse Large B-cell Lymphoma

Other SectionsAbstractIntroductionCase ReportDiscussionConflicts of InterestAuthor ContributionReference

Double-hit and double-expressor primary central nervous system lymphoma: Experience from North India of an infrequent but aggressive variant.

High-grade non-Hodgkin B-cell lymphoma is an aggressive mature B-cell lymphoma that depicts poor treatment response and worse prognosis. The presence of MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements qualifies for triple-hit and double-hit lymphomas (THL/DHL), respectively. We attempted to explore the incidence, distribution, and clinical characteristics of the primary high-grade B-cell lymphoma of the central nervous system (CNS) in our cohort from North India. All the histologically confirmed cases of primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) over a period of 8 years were included. Cases showing MYC and BCL2 and/or BCL6 expression on immunohistochemistry (IHC) (double- or triple-expressor) were further analyzed by fluorescence in situ hybridization for MYC, BCL2 and /or BCL6 rearrangements. The results were correlated with other clinical and pathological parameters, and outcome. Of total 117 cases of PCNS-DLBCL, there were seven (5.9%) cases of double/triple-expressor lymphomas (DEL/TEL) (six double- and one triple-expressor) with median age of 51 years (age range: 31-77 years) and slight female predilection. All were located supratentorially and were of non-geminal center B-cell phenotype. Only triple-expressor case (MYC+/BCL2+/BCL6+) demonstrated concurrent rearrangements for MYC and BCL6 genes indicating DHL (n = 1, 0.85%), while none of the double-expressors (n = 6) showed MYC, BCL2, or BCL6 rearrangements. The mean overall survival of the DEL/TEL was 48.2 days. DEL/TEL and DHL are uncommon in CNS; mostly located supratentorially and are associated with poor outcome. MYC, BCL2, and BCL6 IHC can be used as an effective screening strategy for ruling out double/ triple-expressor PCNS-DLBCLs.

Tendon Cord Rupture of Tricuspid Valve During Chemotherapy for Primary Cardiac Diffuse Large B-Cell Lymphoma.

Tendon Cord Rupture of Tricuspid Valve During Chemotherapy for Primary Cardiac Diffuse Large B-Cell Lymphoma.

B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma.

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells' signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells' signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma.

Diffuse large B-cell lymphoma presenting as sternal mass in a patient with ankylosing spondylitis: a case report study.

The authors present a rare case of primary diffuse large B-cell lymphoma of the sternum in a 41-year-old Iranian woman with ankylosing spondylitis (AS). Physical examination revealed a 7×7.5cm firm swelling of the anterior midline chest wall above the breasts, and MRI showed a lesion within the sternal marrow with an associated soft-tissue mass in the anterior aspect of the sternum. Following core-needle biopsy under ultrasound guidance, a histopathological study demonstrated diffuse sheets of large noncleaved atypical cells with large multilobated prominent nuclei and fine chromatin compatible with diffuse large B-cell lymphoma. Primary and exclusive involvement of the sternum is an uncommon presentation of lymphoma. Radiological, histological, and clinical characteristics of primary bone lymphoma can resemble those of other medical disorders. Although infrequent, existing evidence shows that AS seems to be associated with a small but significant risk for malignancy. Even though inflammatory involvement of the anterior chest wall could be a common clinical finding in patients with AS, it is recommended that anterior chest wall pain or any mass almost always needs comprehensive assessment and imaging evaluation in such patients to avoid any delayed diagnosis, misdiagnosis, and ensuing morbidity or mortality.

Incidental finding of multiple diffuse large B-cell lymphomas masquerading as jejunojejunal intussusception with unexplained pleural effusion: a case report.

This novel case report describes an 84-year-old man with multiple primary diffuse large B-cell lymphomas (DLBCLs) of the jejunum with disseminating pleural and multiple regional lymph nodes involvement presenting as intestinal obstruction and segments of jejunojejunal intussusception. The patient underwent surgical intervention and adjuvant chemotherapy. Unfortunately, the patient suffered from multiple organ failure and died 4 months after surgery. Obstruction and perforation are rare and life-threatening complications of GI lymphoma. Multiple DLBCLs of the jejunum are rare. Moreover, primary GI-DLBCL that initially presents with pleural effusion or with intestinal perforation is uncommon. This report aims to remind clinicians that lymphoma should be considered when assessing the cause of unexplained pleural effusion, especially when the available examination data cannot be confirmed by clinical manifestations. Through this case report, the authors learn that clinical manifestations, morphological characteristics, immunophenotypes, and molecular biological characteristics are vastly different and important. This poses the biggest challenge before surgery and should not be ignored.

Primary Mediastinal Diffuse Large B-Cell Lymphoma presenting with pyrexia of unknown origin in a 13-year-old boy

Primary Mediastinal Diffuse Large B-Cell Lymphoma presenting with pyrexia of unknown origin in a 13-year-old boy

Capturing the Functional Antibody Repertoire from Multiple B-cell Subsets Following Antigen Stimulation.

Abstract Antigen stimulation of mature B-cells induces activated B-cells followed by differentiation to either memory B-cells or plasmablasts. Each subset has a unique phenotype and potentially unique immunoglobulin repertoire that can be mined for therapeutic antibody candidates. As new targets for therapeutic antibodies have become more challenging, primary B-cell technologies have arisen to meet this challenge, but, their use has typically been limited to one of the B-cell subsets. We sought to develop a platform that could be used generally to interrogate all of the B-cell subsets (i.e., activated, memory and plasmablasts) that are potential sources of useful antibodies. Using fluorescence activated cell sorting (FACS), we have identified and sorted antigen-specific activated and memory B-cells by staining for CD19, surface IgG, and fluorochrome-tagged antigen. Antigen-specific plasmablasts have been identified and sorted after encapsulation of cells in microdroplets, capture of secreted IgG, CD19/CD138 staining, and fluorochrome-tagged antigen staining. Additionally, hybridomas have been evaluated using either protocol. The sorted cells have been sequenced by next generation sequencing (NGS) of paired heavy and light chains. With this platform ~10,000–20,000 antigen specific B-cells from a population of a few million viable lymphocytes have been sorted in 1–2 hours. From the sorted population, 100 – 700 unique paired clonotypes have been identified using this platform. The platform enables the capture of immunoglobulin repertoires from multiple B-cell subsets that is comprehensive, flexible, and cost-effective.

Primary B-cell non-Hodgkin lymphoma of the parotid gland: An analysis based on the SEER database.

Primary malignant lymphoma of the parotid gland is a rare entity. The disease is often misdiagnosed, and its survival factors remain unclear. This study included patients diagnosed with primary B-cell non-Hodgkin lymphoma of the parotid gland from 1987 to 2016 in the surveillance, epidemiology, and end results program. Univariate survival analysis was conducted using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazards regression model. A competing risks regression model was applied to estimate the specific risks associated with parotid lymphoma mortality. A total of 1443 patients were identified. The overall survival of indolent primary B-cell lymphoma of the parotid gland was higher than that of aggressive lymphoma (hazard ratio 0.53, 95% confidence interval 0.44-0.64, P < .001), and older patients (≥70 years) exhibited inferior overall survival. Histological subtype and age are important prognostic factors in patients with primary B-cell non-Hodgkin lymphoma of the parotid gland.

Stroke Like Presentation Of CNS Lymphoma (P14-13.005)

<h3>Objective:</h3> To present an unusual case of primary diffuse large B-cell lymphoma of the CNS with stroke-like symptoms, imaging findings and anti-phospholipid antibodies. <h3>Background:</h3> Primary diffuse large B-cell lymphoma of the central nervous system is a rare primary tumor of the brain, that is challenging to diagnose. <h3>Design/Methods:</h3> Case and literature review. <h3>Results:</h3> A 56-year-old man with hypertension, hyperlipidemia, and diabetes presented with acute onset L sided weakness with right midbrain, cerebral peduncle and thalamic increase DWI signal and antiphospholipid antibodies, initially suspected for possible stroke. Close follow up imaging with contrast study was planned due to atypical imaging findings. Patient was discharged to acute rehab on therapeutic Warfarin. Two weeks later, he returned with poor mental status, worsening left sided weakness, numbness, dysarthria and apathy. Repeat MRI brain showed increased DWI signal with increased mass effect. Post contrast MRI brain revealed expansile infiltrative FLAIR and DWI hyperintensity in the right thalamocapsular region extending into the midbrain and anterior cerebellum with superimposed patchy enhancement in the right thalamocapsular area. Findings are suspicious of CNS lymphoma vs high-grade glioma vs inflammatory and infectious processes. Lumbar puncture was non-revealing. A right thalamic biopsy confirmed neoplastic B-cells, positive for Bcl-2, subset Bcl-6 (50%) and MUM-1 (50%), negative for CD10, CD30, and Bcl-, compatible with primary diffuse large B-cell lymphoma of CNS. Immediate treatment with R-MPV regimen (rituximab, methotrexate, procarbazine, vincristine) was started, in addition to solumedrol and whole brain radiation therapy with rapid clinical improvements after steroids treatment before combination chemotherapy. <h3>Conclusions:</h3> Primary CNS lymphoma is a rare and elusive disorder with variable symptoms, signs, clinical courses and images findings that can mimic stroke syndromes and requires vigilance and close follow up for accurate diagnosis and effective treatment. Hypercoagulable state or antiphospholipid antibodies can be associated with large B cell lymphoma. <b>Disclosure:</b> Dr. Sawass Najjar has nothing to disclose. The institution of Dr. Wang has received research support from Maimonides Research &amp; Development Foundation.

A Case of CNS Lymphoma Imitating Post-Vaccination ADEM (P14-13.003)

<h3>Objective:</h3> NA <h3>Background:</h3> A previously healthy 42-year-old male presented acutely with slurred speech, confusion and urinary incontinence several weeks after receiving a COVID booster and Tdap vaccination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> Initial workup revealed multifocal enhancing T2 white matter hyperintensities in the bilateral frontal/parietal lobes, corpus callosum and bilateral midbrain, sparing the cerebellum and spinal cord. Contrast enhanced CT of the chest, abdomen and pelvis showed no masses or lymphadenopathy. Cerebrospinal fluid analysis showed a mild lymphocytic pleocytosis (12) with normal RBC, protein, glucose, negative meningitis/encephalitis PCR, cytology and autoimmune encephalitis antibodies. Serum testing was negative for HIV, RPR, NMO, MOG and antinuclear antibodies. Working diagnosis of acute disseminated encephalomyelitis was made and he was started on IV methylprednisolone 1g daily for 5 days followed by an oral steroid taper with a weekslong improvement in symptoms to his neurologic baseline followed by relapse. We repeated MRI brain which demonstrated mixed response to treatment and two repeat CSF analyses showed 2 WBC with negative cytology. Given symptom recurrence, 1g daily IV methylprednisolone was re-administered for 5 days with another brief improvement, followed by IVIG 2g/kg over 5 days. Despite aggressive immunotherapy, his symptoms continued to worsen, and he was referred for brain biopsy confirming the diagnosis of primary diffuse large B-cell lymphoma of the CNS. At the direction of neuro-oncology, the patient underwent 6 cycles of systemic high-dose methotrexate and rituximab and 2 cycles of temozolomide with PET/MRI evidence of complete response (no lesion enhancement). His performance status improved significantly, and he underwent autologous hematopoietic stem cell transplant for consolidative therapy. <h3>Conclusions:</h3> CNS lymphoma should be considered in the differential for contrast-enhancing FLAIR hyperintensities and can be steroid responsive. Brain biopsy should not be delayed in cases where CNS lymphoma is a leading differential as it can guide early disease management and help improve patient outcomes. <b>Disclosure:</b> Dr. Frank has nothing to disclose. Dr. Alalami has nothing to disclose. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of an immediate family member of Dr. Livingston has received research support from Vertex. The institution of an immediate family member of Dr. Livingston has received research support from Roche. The institution of an immediate family member of Dr. Livingston has received research support from AstraZeneca. The institution of an immediate family member of Dr. Livingston has received research support from Enanta. Dr. Hu has nothing to disclose. Dr. Shadbehr has nothing to disclose.