System Lymphoma Research Articles

Anaplastic lymphoma kinase-negative primary systemic anaplastic large cell lymphoma mimicking a ruptured epidermal cyst of the scalp: a case report and literature review

Anaplastic lymphoma kinase-negative primary systemic anaplastic large cell lymphoma mimicking a ruptured epidermal cyst of the scalp: a case report and literature review

Assessing the intracranial metabolic score as a novel prognostic tool in primary CNS lymphoma with end of induction-chemotherapy 18F-FDG PET/CT and PET/MR.

The metabolic response of primary central nervous system lymphoma (PCNSL) patients has yet to be evaluated. This study aimed to assess the prognostic value of a novel scoring scale, the intracranial metabolic score (IMS), in PCNSL patients receiving end-of-therapy 18F-FDG PET/CT (EOT-PCT) and PET/MR (EOT-PMR). The IMS was determined based on the metabolism of normal intracranial structures, including gray matter, white matter, and cerebrospinal fluid. The EOT-PCT cohort was evaluated using the IMS and commonly used Deauville score (DS). Another cohort of patients who underwent the EOT-PMR was used to validate the accuracy of the IMS. In total, 83 patients were included in the study (38 in PET/CT cohort, and 45 in PET/MR cohort). The area under the curve (AUC) values of the IMS for predicting PFS and OS were superior to those of the DS. When patients in the PET/CT cohort were stratified into five groups (respectively labeled IMS 1-5), three groups (IMS1-2, IMS 3-4, and IMS 5), or two groups (IMS1-3 and IMS4-5; IMS 1-4 and IMS 5), a higher IMS score was significantly correlated with poorer PFS and OS (p < 0.001). Similar results were observed for PFS in the PET/MR cohort (p < 0.001). The IMS and DS scale were found to be independent prognostic indicators for PFS and OS in the PET/CT cohort, and the IMS was identified as the sole independent prognostic indicator for PFS in the PET/MR cohort. The IMS as a novel and effective prognostic tool for PCNSL patients, showing superior predictive value for patients' outcomes compared to the DS when assessed with EOT-PET scans.

SURG-26. IMPROVEMENT IN PRECISION AND SURGICAL EFFICIENCY USING THE STEALTH AUTOGUIDE™

Abstract INTRODUCTION The Stealth Autoguide™ (Medtronic) automatically determines the path for guiding instruments based on the created surgical plan. It seamlessly integrates continuous real-time navigation with robotic alignment capabilities, enhancing intraoperative workflow efficiency and supporting precise positioning. Our institution has achieved favorable results with surgeries utilizing the Stealth Autoguide™, and we report these outcomes and our future prospects. METHODS We conducted 15 surgeries at our institution using the StealthStation S8 (Medtronic) linked with the Stealth Autoguide™. The average age was 56.2 years, with 10 males and 5 females, all under general anesthesia. RESULTS The cases included 11 gliomas, 2 primary central nervous system lymphomas, 1 germ cell tumor, and 1 brain abscess. Applications of the Stealth Autoguide™ included 7 biopsies (6 burr holes, 1 craniotomy), 6 placements of fenestrations, and 2 tubing placements. The biopsies allowed for quick and reliable tissue sampling. In fenestration cases, it was possible to position quickly and precisely at the target, placing it at the planned site with high accuracy. Additionally, by using a 3D endoscopic system, surgeons could view both the surgical field and navigation screens simultaneously without shifting their gaze, enhancing safety during procedures. In the case of an intraventricular germ cell tumor, tubing preceded by ViewSite™ allowed for a safe and clear surgical field. CONCLUSION Surgeries using the Stealth Autoguide™ were conducted safely and efficiently, regardless of the surgical technique, achieving high-precision positioning. Continuing to utilize this system is expected to improve the accuracy, safety, and reproducibility of surgeries, thereby reducing the burden on patients.

CTNI-12. TIRABRUTINIB FOR RECURRENT/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA –A SINGLE-INSTITUTION RETROSPECTIVE ANALYSIS–

Abstract BACKGROUND Tirabrutinib is a second-generation, highly selective oral Bruton’s tyrosine kinase inhibitor and approved for the treatment of recurrent/refractory primary central nervous system lymphoma (PCNSL) in Japan. We reviewed our single institution experiments of tirabrutinib. MATERIALS AND METHODS Our institutional review board approved this retrospective study. Twenty-eight patients with recurrent or refractory PCNSL treated with tirabrutinib at our institution between 2020 and 2024 were included. Information regarding the patient’s age, gender, imaging findings, pathological results, including immunostaining findings, and treatment information, including chemotherapy and radiation therapy, was obtained from medical records. RESULTS Tirabrutinib was administered to 14 patients with recurrent cases (20-85 years old, median 69.5 years old, 9 males and 5 females), 14 with refractory cases (59-87 years old, median 74 years old, 9 males and 5 females). Three male patients received rechallenge with tirabrutinib against re-relapsed. We assessed the effectiveness of tirabrutinib and observed complete response (CR) in 12 cases, partial response (PR) in 1 case, and progressive disease (PD) in 1 case among refractory patients. In recurrent cases, we observed CR in 8 cases, PR in 1 case, stable disease (SD) in 3 cases, and PD in 2 cases. In rechallenge for re-relapsed cases, we observed CR in 2 cases and PD in 1 case. The progression-free survival following beginning of tirabrutinib was 12.95 months for refractory cases and 8.2 months for recurrent cases. The overall survival was 25 months for refractory cases and 12.8 months for recurrent cases. One patient each experienced CTCAE grade 3 interstitial pneumonia or liver failure, both of which improved after discontinuing the medication. Four patients exhibited grade 1-2 skin rashes. CONCLUSIONS Tirabrutinib demonstrates efficacy and high tolerability for the treatment of recurrent/refractory PCNSL in real-world settings.

INNV-20. FLUORESCEIN GUIDED SURGERY FOR ATYPICAL BRAIN LESIONS: IS IT USEFULL? CASE SERIES USING A LOW-COST DEVICE

Abstract INTRODUCTION Sodium Fluorescein (SF) enhances in areas in the brain with a disrupted Blood brain barrier (BBB). In neurosurgery, SF is extensive used for malignant brain tumors. Solitary brain abscesses (BA) are characterized by the pathognomonic finding of BBB disruption. Consequently, FL may have the potential to improve the intra-operative visualization of BA. Other infections also disrupt BBB and SF may guide these surgeries. CASE SERIES A 32-year old male patient, previously diagnosed with HIV presented with headache and during investigation MRI disclosure an extensive leptomeningeal commitment. Leptomeningeal biopsy guided by fluorescein and using Varioguide system was performed and the diagnosis was primary central nervous system lymphoma (Diffuse large B-cell). During surgery, it was observed increased fluorescence in arachnoid. A 72-year old woman presented with headache, impairment of mental status and epilepsy and a KPS of 60. Her initial hypothesis was metastasis but patient did not have a primary situs diagnosis. An open biopsy was performed through temporal posterior craniotomy. During surgery no visible well delimited tumor was found, even with ultrasound use. Fluorescein guided biopsy was performed. Histological evaluation showed an Epstein-Barr virus infection causing encephalitis. This is an extremely rare presentation of this type of infection and SF was extremely helpful to guide the procedure. CONCLUSION This paper reported atypical uses of SF for brain mass lesions surgeries. One of our cases is a unique presentation of a virus encephalitis which mimicked metastasis and other of increased fluorescence in Lymphoma. These atypical use of SF are relevant for further neurosurgical plannings Keywords: Fluorescein, Lymphoma, Biopsy

CTIM-35. PD-1 BLOCKADE WITH CAMRELIZUMAB IN RELAPSED/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

Abstract Primary central nervous system lymphoma (PCNSL) are rare extranodal large B-cell lymphomas. There are no standard-of-care treatment options for patients with relapsed and refractory PCNSL and the overall prognosis is poor. We conducted a phase 2 clinical trial to evaluate the efficacy and adverse events of PD-1 antibody camrelizumab in relapsed/refractory PCNSL. Enrolled patients received camrelizumab 200mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR). Here we present results of 20 relapsed PCNSL patients who treated with camrelizumab. Among them,12 were male and 8 were female. The median age was 57 years (range 25-67 years). Fourteen patients were available to evaluate efficacy. After camrelizumab treatment, 4 got complete response (CR), 3 got partial response (PR), 1 got stable disease, and 6 got progressed disease (PD). The ORR was 50%. The median progression-free survival (PFS) was 19.3 weeks (95% CI, 3.1-35.5). 24 week PFS rate was 40%. For the 7 patients who got CR/PR, got a long sustained response, with a median PFS of 93.6 weeks (range 17-211.6+ weeks). One patient developed pseudoprogression 2 months after initiation of treatment. By the last follow-up, 18 patients discontinued treatment (10 PD, 4 complete treatment, 3 withdrawal of informed consent, 1 lost follow-up). Eleven patient got PD. Nine patients received chemotherapy and 5 received radiotherapy after PD. PD-L1 expression, microsatellite stability and mutation burden of the tumors were detected in 9 patients, and all the three factors were not correlated with efficacy. The main drug-related adverse reaction was cutaneous capillary hyperplasia. None of the patients dropped out of the study due to adverse reactions. Our data suggest that camrelizumab is active in relapsed/refractory PCNSL and support further investigation of PD-1 blockade in PCNSL.

QLTI-17. COMPARATIVE ANALYSIS OF LUMBAR PUNCTURE UTILITY IN DIAGNOSIS OF PRIMARY VERSUS SECONDARY CNS LYMPHOMA: A RETROSPECTIVE STUDY

Abstract OBJECTIVES Central nervous system lymphoma (CNSL) is a subtype of non-Hodgkin lymphoma, which affects the brain, spinal cord, leptomeninges, or eyes. It includes primary (PCNSL) and secondary CNSL (SCNSL). CNSL diagnosis relies on neuroimaging, cerebrospinal fluid (CSF) analysis (cytology, flow cytometry), and/or tissue biopsy. Lumbar punctures (LP) aid in investigating leptomeningeal involvement. Positive findings confirm CNS involvement and guide treatment decisions. This study seeks to determine the effectiveness of CSF analysis via LP in diagnosing SCNSL compared to PCNSL. METHODS This retrospective study comprised patients who received treatment with HD-MTX treated at our center from July 2020 to January 2024. Data was retrospectively collected from electronic medical records (EMR). Pathology reports from tissue biopsy and enhancement of CNS visualized on imaging were utilized to diagnose and differentiate PCNSL and SCNSL. CNS cytology and flow cytometry from LP were analyzed to determine the diagnostic accuracy of LP CSF cytology results in diagnosing CNSL. Descriptive statistical and comparative analysis was conducted to analyze the results. RESULTS The sample included 70 patients, 35 each diagnosed with PCNSL and SCNSL. Of these, only 49 patients underwent LP, with a significantly higher proportion of patients in the SCNSL group, 33 (67%), compared to the PCNSL group, 16 (33%) (P&amp;lt;0.001). Among those who underwent LP, CSF cytology and/or flow cytometry were positive in 19 cases, with significantly higher detection rates among the SCNSL cases (16 of 33, 48.5%) compared to the PCNSL cases (3 of 16, 18.8%; p=0.045). CONCLUSION Our findings indicate that LPs play a crucial role in diagnosing SCNSL, with a significantly higher CSF detection rate than PCNSL. LP has a limited impact on diagnosing PCNSL, suggesting that tissue biopsy should be prioritized to avoid increased time for PCNSL diagnosis. This study underscores the importance of tailored diagnostic approaches for suspected PCNSL and SCNSL, emphasizing the utility of LP in diagnosing SCNSL and tissue biopsy for PCNSL.

CTNI-33. EARLY COMPLETE RESPONSE MIGHT NOT BE AN INDICATOR OF LONGER PROGRESSION-FREE SURVIVAL IN NEWLY-DIAGNOSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA WITH A COMPLETE RESPONSE BY MTX-BASED INDUCTION THERAPY

Abstract Primary central nervous system lymphoma (PCNSL) is an extra-nodal non-Hodgkin lymphoma solely arising from the central nervous system including eyes. While 70% of patients with newly-diagnosed PCNSL achieve a complete response (CR) after R-MPV, the current standard of care MTX-based induction therapy, recurrence yet frequently occurs (~50%) and clinical factors related to failure are not well defined. Early complete response is associated with lower recurrence rate in various cancers. In this study, we conducted a retrospective, single-institution study to investigate whether early complete response was associated with recurrence in PCNSL. Newly-diagnosed PCNSL patients treated with R-MPV at the authors’ institution between 2011 and 2022 were identified, and progression-free survival (PFS), overall survival (OS) were analyzed along with number of chemotherapy cycles required to achieve a CR or CR unconfirmed (CRu). In total of 92 patients treated with R-MPV identified, 68 (75%) patients achieved a CR or CRu. Among patients who achieved CR or CRu, a median total of seven (1-8) R-MPV cycles were delivered. The median cycle required to achieve CR or CRu was five (1-8). Consolidation whole brain radiation therapy (WBRT) was given to 29 younger patients (median age: 63), while 39 older patients (median age: 74) were treated without WBRT. The number of chemotherapy cycles required to achieve CR or CRu was not associated with PFS or OS in all ages. However, requiring six or more chemotherapy cycles to achieve CR or CRu was associated with longer PFS (p=0.046) in patients treated without WBRT. These data suggest that early complete response might not be indicative of superior survival outcome in newly-diagnosed PCNSL treated without consolidation WBRT. Persisting enhancing lesions during chemotherapy could lead to treatment intensification through delivering greater number of chemotherapy cycles, which might have conferred longer PFS in these patients.

RADT-39. CENTRAL NERVOUS SYSTEM BRIDGING RADIOTHERAPY (CNS-BRT) ACHIEVES RAPID CYTOREDUCTION PRIOR TO CAR T-CELL THERAPY FOR AGGRESSIVE B-CELL LYMPHOMAS

Abstract BACKGROUND CAR T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extra-cranial lymphoma to improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that CNS-BRT would achieve similar, significant cytoreduction prior to CART for CNSL. METHODS We analyzed CNSL patients with non-Hodgkin B-cell lymphomas who received CNS-BRT prior to commercial CART. Best CNS response post-CART was evaluated using the International Primary CNS Lymphoma Collaborative Group (IPCG) or RANO for parenchymal or leptomeningeal lesions, respectively. Cytoreduction from CNS-BRT was calculated as change in lesion size prior to CART. RESULTS Twelve patients received CNS-BRT, with median follow up of 11.8m (IQR: 8.5–21.9). Ten had CNSL (9 secondary, 1 primary) and 2 patients had epidural disease (evaluable for toxicity). All ten CNSL patients had progressive disease at the time of CNS-BRT. RT targets included whole brain (n=3), involved site (partial) brain (n=4), involved site spine (n=4), and orbits (n=1) with median dose 24Gy (range: 15-33). 1/12 patients experienced grade ≥3 cytokine release syndrome (CRS), and 3/12 patients experienced grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS). CNS-BRT achieved a 74.0% (95%CI: 62.0–86.0) mean reduction in lesion size from baseline (p=0.014) at a median of only 12d from BRT completion and pre-CART infusion. Best CNS response included 8 complete responses (CR), 1 partial response (PR), and 1 progressive disease (PD). Three patients experienced CNS relapse outside the BRT field for a 12-month estimated risk of CNS progression post-CART of 20.0% (95%CI: 3–49). CONCLUSIONS Early data suggest CNS-BRT achieves rapid cytoreduction and favorable CNS response. The rates of severe CRS/ICANS were similar to comparison series of CNSL patients treated with CART without BRT suggesting an acceptable safety profile. Our data support further study of BRT as a bridging strategy for CNSL-directed CART.

Clinical outcomes of chimeric antigen receptor T-cell therapy following autologous hematopoietic stem cell transplantation in 38 patients with refractory/relapsed primary or secondary central nervous system lymphoma.

Several reports have indicated that chimeric antigen receptor (CAR) T-cell therapy following autologous hematopoietic stem cell transplantation (ASCT) is a promising strategy for refractory/relapsed (r/r) central nervous system lymphoma (CNSL), but the number of reported cases is limited. The cohort in this retrospective study consisted of 38 patients with r/r CNSL who received CAR T-cell therapy following ASCT at our center between January 2019 and April 2024. Group comparisons of continuous variables were tested using the unpaired Student's t-test or the Mann-Whitney U-test, while categorical variables were analyzed using Fisher's exact test. The Kaplan-Meier method was employed to estimate survival curves, and group comparisons were performed using the log-rank test. The cohort comprised 38 patients with r/r CNSL, all of whom had active CNS involvement. After therapy, the best overall response rate (ORR) of all patients was 78.9%. Subgroup analysis found that a lower ORR was observed in patients with lactate dehydrogenase levels above the upper limit of normal (60.0% vs. 91.3%, P = 0.039). With a median follow-up of 37.5months, the estimated 1-year overall survival (OS) and progression-free survival (PFS) rates were 72.8% and 57.4%, respectively. The risk factors associated with PFS was no response to current therapy (adjusted hazard ratio: 22.87, P < 0.001). The incidence rates of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were both 13.2%. Among the 25 patients with secondary CNSL (SCNSL), the best ORRs were 91.7% for those with CNS lesions only and 61.5% for those with CNS and systemic lesions (P = 0.160), while the estimated 1-year PFS rates were 83.3% and 38.5%, respectively (P = 0.030). CAR T-cell therapy following ASCT shows promising efficacy for r/r CNSL patients. Besides, SCNSL patients with CNS and systemic lesions have inferior treatment efficacy compared to those with CNS lesions only.

CTNI-38. SINGLE-CENTER COMPARATIVE ANALYSIS ABOUT OUTCOMES OF MULTI-AGENTS CHEMOTHERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; R-MPV SHOWED A FAVOR RESULT

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a malignant tumor in the brain, spinal cord, and eyes. Radiotherapy may cause delayed leukoencephalopathy so that the first-line treatment is methotrexate (MTX)-based multi-agent chemotherapy. We had used the Bonn protocol based on MTX and cytarabine, but since 2020, we have adopted the R-MPV protocol. This study analyzes the outcomes of patients treated initially at our institution. METHODS AND RESULTS We reviewed 57 out of 88 newly diagnosed PCNSL patients treated with chemotherapy alone between December 2005 and January 2023. Initial treatments included the Bonn protocol in 25 patients (12 with rituximab, forming R-Bonn) and R-MPV in 26 patients. High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) was given as consolidation in 4 Bonn and 9 R-MPV patients. The Bonn protocol was completed by 20 patients (80%) with a complete response (CR) in 19 (76%). The R-MPV protocol was completed by 23 patients (88%) with CR in 22 (85%). Post-treatment outcomes were compared using survival analysis. Median progression-free survival (mPFS) had not been reached in the R-MPV group and was significantly better than 33.1 months in the Bonn protocol and 58.6 months in the R-Bonn protocol (log-rank test; p=0.0296, 0.0036). Overall survival (OS) did not show significant differences. PBSCT’s impact on outcomes suggested improvement in PFS and OS after R-MPV, but this was not statistically significant. DISCUSSION We examined the efficacy of different chemotherapy regimens for PCNSL at our institution. The R-MPV protocol showed superior completion rates, response rates, and treatment efficacy. Consolidation with PBSCT may improve outcomes, though further investigation with more cases and longer observation is necessary.

RADT-12. DERIVING IMAGING BIOMARKERS FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA USING DEEP LEARNING

Abstract PURPOSE Primary central nervous system lymphoma (PCNSL) is typically treated with chemotherapy, steroids, and/or whole brain radiotherapy (WBRT). Determining which patients benefit from WBRT after chemotherapy and which are adequately treated with chemotherapy alone remains a clinical challenge. Although WBRT is associated with improved outcomes, it also carries a risk of neurocognitive side effects. This study aims to refine PCNSL patient phenotyping by leveraging deep learning (DL) extracted imaging biomarkers to enable personalized therapy. METHODS Our study included 71 patients treated between 2009-2021. The primary outcome of interest was overall survival (OS) assessed at one- and two-year cutoffs. The DL model leveraged an 8-layer 2D convolutional neural network analyzing individual slices of post-contrast T1-weighted pre-treatment MRI scans. Survival predictions utilized a weighted voting system related to tumor size. Model performance was assessed with accuracy, sensitivity, specificity, and F1 scores. Time-dependent AUCs were calculated and C-statistics were computed to summarize the results. Kaplan-Meier (KM) survival analysis assessed differences between low and high-risk groups and were evaluated using the log-rank test. RESULTS The cohort’s average age was 65.6 years with average OS of 2.80 years. For one-year OS, the model achieved an AUC of 0.73 (0.60-0.85), accuracy of 0.73 (0.61-0.82), sensitivity of 0.72 (0.54–0.85), and specificity of 0.73 (0.58–0.84). For two-year OS, the model achieved an AUC of 0.70 (0.58-0.82), accuracy of 0.70 (0.58-0.79), sensitivity of 0.68 (0.55–0.81), and specificity of 0.71 (0.55–0.84). Model performance is presented with respective 95% confidence intervals. KM curves showed the one and two-year models effectively discriminated between low- and high-risk group, reporting c-statistics of 0.73 (p&amp;lt;.001) and 0.71 (p&amp;lt;.001) respectively. A sub-analysis confirmed consistent model performance across different tumor volumes and focality. CONCLUSION DL classifiers of PCNSL MRIs can stratify patient phenotypes beyond traditional risk paradigms. Given dissensus surrounding PCNSL treatment, DL can augment risk stratification and treatment personalization, especially with regards to WBRT decision making.

Epidemiologic trends and survival outcomes in patients with primary digestive system lymphoma in the United States.

Primary digestive system lymphoma (PDSL) is an important entity of extranodal lymphoma, yet updated epidemiologic and survival data are lacking. Patients diagnosed with PDSL between 1975 and 2020 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis estimated survival outcomes. Multivariable Cox regression identified independent risk factors, and nomograms were developed to predict 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS). A total of 30,568 patients with PDSL were identified, with 57.9% being male and 80.4% white. The most frequent tumor site was the stomach (48.7%) and diffuse large B-cell lymphoma (DLBCL) was the predominant histologic subtype (45.0%). The overall incidence from 2016 to 2020 was 11.11 per 1,000,000 persons, with a decrease observed in lymphoma rates for the stomach, small intestine, large intestine, and pancreas. Long-term trends showed an initial rise in PDSL incidence, followed by a decline since the 1990s. The median OS across all patients was 103months, with appendiceal lymphoma showing the highest median OS of 253months. Factors including diagnosis year, age, sex, race, primary tumor site, histologic subtype, stage, and treatment modalities were significantly associated with OS and CSS. Nomograms achieved C-indices of 0.720 for OS and 0.723 for CSS in the training cohort. The incidence of PDSL initially increased but has recently declined. Survival for all PDSL patients has improved over time. Nomograms to predict survival for patients with DLBCL exhibited good predictive and discriminating abilities.

The utilization of cytology for intraoperative diagnosis of primary central nervous system lymphoma

To investigate the diagnostic value of intraoperative cytology and rapid immunocytochemistry in primary central nervous system lymphoma. 254 cases of lymphoma and 82 cases of non-lymphoma were collected from 2010 to 2023. Frozen section(FS) was using alone in 44 cases during 2010–2014, FS and intraoperative cytology(IC) were using in 251 cases during 2015 to 2022. Rapid immunocytochemical(RICC, CD20, GFAP) were using with FS + IC in 41 cases during 2021 to 2023. Method One: According to the results of archives, statistic the diagnostic accuracy of lymphoma during three time periods. Method Two: All cases were randomly renumbered, 4 neuropathologists compared the accuracy of independent histology and that of combining cytology. The archives showed the diagnostic accuracy of FS in PCNSL was 77.27%, FS + IC was 86.06%, FS + IC + RICC was 92.68%. The retrospective study demonstrated the diagnostic accuracy of FS was 79.76%, FS + IC was 87.33% and FS + IC + RICC was 92.68%. The positive predictive value, negative predictive value, sensitivity, specificity and accuracy of CD20 were 100%, 76.92%, 90.32%, 100% and 92.68%, respectively. The results of the paired χ2 test was no statistically significant difference (0.05 < P < 0.1) between FS + IC + RICC and immunohistochemical (IHC) diagnosis of paraffin sections. The integration of IC + RICC + FS diagnosis can significantly enhance the intraoperative diagnostic accuracy of PCNSL and rectify potential errors that may occurred when relying solely on FS diagnosis.

Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: a case series

Abstract Introduction Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients. Results Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX). Methods We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL. Conclusion Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma

Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma

An update on EBV-related cutaneous lymphoproliferative disorders: a systematic review.

Epstein Barr virus (EBV) positive B lymphoproliferative disorders (LPD) with cutaneous involvement include a series of rare entities that go from indolent processes to aggressive lymphomas. Since the latest WHO-EORTC classification of cutaneous lymphomas in 2018, significant changes have been included in the new classifications of hematological malignancies. B-cell EBV+ LPD mainly affect immunocompromised patients while T-cell EBV+ LPD are more prevalent in specific geographic regions such as Asia, Central America, and South America. This systematic review summarizes the main clinical, histological, immunophenotypic and molecular characteristics of B- and T-cell EBV+ LPD that may compromise the skin at diagnosis. B-cell EBV+ LPD include primary cutaneous lymphomas such as EBV-MCU, as well as cutaneous systemic lymphomas that may present such as lymphomatoid granulomatosis (LG), EBV+ diffuse large B cell lymphoma, NOS, plasmablastic lymphoma (PBL), and extracavitary primary effusion lymphoma (EC-PEL). EBV+, EBV-positive polymorphic B cell LPD, or post-transplant lymphoproliferative disorders (PTLD). Regarding T-cell EBV+ LPD, most of these entities are categorized within T/NK-cell lymphoproliferative processes and lymphomas of childhood, including extranodal T/NK lymphoma, and even more exceptional forms such as EBV-positive T-cell centrofollicular lymphoma and intravascular T/NK-cell lymphoma. Diagnosis is based on integrating the clinical, histological, immunohistochemical, and genetic criteria discussed throughout this article. Management is multidisciplinary, posing a challenge for dermatologists and hematologists involved in the management of these patients. Having scientific evidence available in this field is of paramount importance because overtreatment must be carefully avoided.

MRI-based Radiomics Virtual Biopsy for BCL6 in Primary Central Nervous System Lymphoma

AimTo establish machine learning model based on radiomic signature for predicting B-cell lymphoma 6 (BCL-6) rearrangement in primary central nervous system lymphoma (PCNSL). Materials and MethodsRetrospective study on 102 PCNSL patients (31 with BCL-6 rearrangement positive, 71 with BCL-6 rearrangement negative) were randomly divided into the training and validation set at a ratio of 7:3. Radiomics models based on contrast-enhanced T1-weighted imaging (CE-T1WI) and fluid-attenuated inversion recovery (FLAIR) in different regions including VOItumor core and VOIperitumoral edema. Radiomics features were extracted and selected using LASSO regression, and radiomics score (rad-score) were calculated using the weighted coefficients. Four machine learning models (logistic regression, random forest, support vector machine, K-nearest neighbors) were developed and evaluated based rad-score. The optimal radiomics model was integrated into the clinical or radiological factors to construct a predictive model through logistic regression analysis. A nomogram was constructed based on independent significant features for individualized prediction. ResultsAll rad-scores based on CE-T1WI and FLAIR sequences were significantly associated with BCL6 rearrangement (p<0.05) in univariate regression analysis. LR machine learning model performed best with AUCs of 0.935 (training) and 0.923 (validation). Rad-scores from CE-T1WI tumor core and peritumoral edema were independent significant predictors. ConclusionRadiomics signature based on CE-T1WI and FLAIR sequences have significant value in distinguishing BCL6 rearrangement. The CE-T1WI radiomics model based on VOItumor core and VOIperitumoral edema are robust markers for identifying BCL6 rearrangement.

Distinguishing clinical and imaging characteristics of primary central nervous system lymphoma from high-grade glioma and metastatic brain tumors.

The purpose of this retrospective analysis was to evaluate the clinical presentations, radiological characteristics, patient outcomes, and therapeutic approaches among individuals diagnosed with primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and metastatic brain tumors (METS). We assembled a cohort of brain tumor patients from two medical centers, with two oncologists independently reviewing their clinical profiles. A retrospective examination of 87 PCNSL, 87 HGG, and 71 METS cases was performed to assess the aforementioned parameters. Notable variations were identified in the incidence of epileptic seizures and cognitive impairments between PCNSL and METS patients. Cerebral hemisphere involvement was predominantly observed in HGG and METS cases. PCNSL cases exhibited a higher likelihood of multiple lesions, whereas HGG showed a greater tendency for recurrence. The median survival times were established at 24.3months for PCNSL, 44.5months for HGG, and 27.1months for METS patients. In PCNSL cases, the number of lesions was identified as a significant predictor of mortality (P = 0.008). Our findings highlight the importance of clinical and imaging features in diagnosing PCNSL, which may present distinct features compared to HGG and METS.

CAR T-cell Therapy for Central Nervous System Lymphoma.

While anti-CD19 CAR T-cell therapy represents a major advance in systemic diffuse large B-cell lymphomas, central nervous system (CNS) lymphomas have been excluded from pivotal trials because of the fear of neurotoxicity. The purpose of this review was to assess the efficacy and tolerance of CAR T-cells in CNS lymphomas based on recently published studies. All the studies on CAR T-cell therapy for both primary and secondary CNS lymphomas reported high response rates (complete response rates ranging from 32 to 67%) in highly pre-treated patients. One-year PFS reached 40 to 60% in several studies. Neurotoxicity occurred in 36 to 68% of patients, including grade 3-4 neurotoxicity in 4.5 to 29% of patients. CAR T-cell therapy appears to be a very promising treatment in CNS lymphomas, with efficacy results close to those observed in systemic lymphomas. The toxicity profile, notably regarding neurotoxicity, is reassuring and should not prevent the development of CAR T-cells in the disease.