MYD88 mutation-positive indolent B-cell lymphoma with CNS involvement: Bing-Neel syndrome mimickers.

MYD88 p.L265P mutation occurs in over 90% of Waldenström's macroglobulinemia (WM), which is characterized by lymphoplasmacytic lymphoma (LPL) with monoclonal IgM. WM requires careful diagnosis due to overlapping features with other B-cell malignancies. Bing-Neel syndrome (BNS), a rare complication of WM, involves central nervous system (CNS) invasion. This report describes two cases of morphologically low-grade B-cell lymphoma in the bone marrow accompanied by the presence of a large B-cell lymphoma in the brain and a common MYD88 p.L265P mutation, which were eventually established as BNS mimickers. Although the two components in these cases showed the same identical light-chain restriction, different immunoglobulin heavy-chain rearrangement peaks indicated distinct lymphoma stem cells for CNS and bone marrow lesions. These clinical cases emphasize the challenges in diagnosing BNS. Based on the findings, biopsy is recommended for accurate identification of the clonal relationship and MYD88 mutation status.

Radiomic prediction for durable response to high-dose methotrexate-based chemotherapy in primary central nervous system lymphoma.

BACKGROUND: The rarity of primary central nervous system lymphoma (PCNSL) and treatment heterogeneity contributes to a lack of prognostic models for evaluating posttreatment remission. This study aimed to develop and validate radiomic-based models to predict the durable response (DR) to high-dose methotrexate (HD-MTX)-based chemotherapy in PCNSL patients. METHODS: A total of 159 patients pathologically diagnosed with PCNSL between 2011 and 2021 across two institutions were enrolled. According to the NCCN guidelines, the DR was defined as the remission lasting ≥1 year after receiving HD-MTX-based chemotherapy. For each patient, a total of 1218 radiomic features were extracted from prebiopsy T1 contrast-enhanced MR images. Multiple machine-learning algorithms were utilized for feature selection and classification to build a radiomic signature. The radiomic-clinical integrated models were developed using the random forest method. Model performance was externally validated to verify its clinical utility. RESULTS: A total of 105 PCNSL patients were enrolled after excluding 54 cases with ineligibility. The training and validation cohorts comprised 76 and 29 individuals, respectively. Among them, 65 patients achieved DR. The radiomic signature, consisting of 8 selected features, demonstrated strong predictive performance, with area under the curves of 0.994 in training cohort and 0.913 in validation cohort. This signature was independently associated with the DR in both cohorts. Both the radiomic signature and integrated models significantly outperformed the clinical models in two cohorts. Decision curve analysis underscored the clinical utility of the established models. CONCLUSIONS: This radiomic signature and integrated models have the potential to accurately predict the DR to HD-MTX-based chemotherapy in PCNSL patients, providing valuable therapeutic insights.

Differentiation between multifocal CNS lymphoma and glioblastoma based on MRI criteria.

PURPOSE: Differentiating between glioblastoma (GB) with multiple foci (mGB) and multifocal central nervous system lymphoma (mCNSL) can be challenging because these cancers share several features at first appearance on magnetic resonance imaging (MRI). The aim of this study was to explore morphological differences in MRI findings for mGB versus mCNSL and to develop an interpretation algorithm with high diagnostic accuracy. METHODS: In this retrospective study, MRI characteristics were compared between 50 patients with mGB and 50 patients with mCNSL treated between 2015 and 2020. The following parameters were evaluated: size, morphology, lesion location and distribution, connections between the lesions on the fluid-attenuated inversion recovery sequence, patterns of contrast enhancement, and apparent diffusion coefficient (ADC) values within the tumor and the surrounding edema, as well as MR perfusion and susceptibility weighted imaging (SWI) whenever available. RESULTS: A total of 187 mCNSL lesions and 181 mGB lesions were analyzed. The mCNSL lesions demonstrated frequently a solid morphology compared to mGB lesions, which showed more often a cystic, mixed cystic/solid morphology and a cortical infiltration. The mean measured diameter was significantly smaller for mCNSL than mGB lesions (p < 0.001). Tumor ADC ratios were significantly smaller in mCNSL than in mGB (0.89 ± 0.36 vs. 1.05 ± 0.35, p < 0.001). The ADC ratio of perilesional edema was significantly higher (p < 0.001) in mCNSL than in mGB. In SWI / T2*-weighted imaging, tumor-associated susceptibility artifacts were more often found in mCNSL than in mGB (p < 0.001). CONCLUSION: The lesion size, ADC ratios of the lesions and the adjacent tissue as well as the vascularization of the lesions in the MR-perfusion were found to be significant distinctive patterns of mCNSL and mGB allowing a radiological differentiation of these two entities on initial MRI. A diagnostic algorithm based on these parameters merits a prospective validation.

Multicenter investigation of preoperative distinction between primary central nervous system lymphomas and glioblastomas through interpretable artificial intelligence models.

OBJECTIVE: Research into the effectiveness and applicability of deep learning, radiomics, and their integrated models based on Magnetic Resonance Imaging (MRI) for preoperative differentiation between Primary Central Nervous System Lymphoma (PCNSL) and Glioblastoma (GBM), along with an exploration of the interpretability of these models. MATERIALS AND METHODS: A retrospective analysis was performed on MRI images and clinical data from 261 patients across two medical centers. The data were split into a training set (n = 153, medical center 1) and an external test set (n = 108, medical center 2). Radiomic features were extracted using Pyradiomics to build the Radiomics Model. Deep learning networks, including the transformer-based MobileVIT Model and Convolutional Neural Networks (CNN) based ConvNeXt Model, were trained separately. By applying the "late fusion" theory, the radiomics model and deep learning model were fused to produce the optimal Max-Fusion Model. Additionally, Shapley Additive exPlanations (SHAP) and Grad-CAM were employed for interpretability analysis. RESULTS: In the external test set, the Radiomics Model achieved an Area under the receiver operating characteristic curve (AUC) of 0.86, the MobileVIT Model had an AUC of 0.91, the ConvNeXt Model demonstrated an AUC of 0.89, and the Max-Fusion Model showed an AUC of 0.92. The Delong test revealed a significant difference in AUC between the Max-Fusion Model and the Radiomics Model (P = 0.02). CONCLUSION: The Max-Fusion Model, combining different models, presents superior performance in distinguishing PCNSL and GBM, highlighting the effectiveness of model fusion for enhanced decision-making in medical applications. CLINICAL RELEVANCE STATEMENT: The preoperative non-invasive differentiation between PCNSL and GBM assists clinicians in selecting appropriate treatment regimens and clinical management strategies.

Primary Central Nervous System Lymphoma Presenting as a Solitary Fourth Ventricular Mass: A Case Report.

The occurrence of primary fourth ventricular lymphoma is an exceptionally uncommon phenomenon. Here, we present a case of lymphoma in the fourth ventricle in a 30-year-old male who presented with progressive headache and vertigo over the last one month of his presentation. Preoperative MRI revealed a space-occupying lesion of the fourth ventricle. Pathological analysis following complete resection confirmed the lesion as primary central nervous system lymphoma. The patient underwent chemotherapy following the MTR (methotrexate, temozolomide, and rituximab) protocol with four months of uneventful follow-up, indicating no disease recurrence. Therefore, clinicians are advised to consider the potential presence of lymphoma as part of the differential diagnosis for space-occupying lesions, especially when there is a combination of clinical deterioration and rapid imaging progression.

Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.

BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors.

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

Long-term remission with temozolomide for AIDS-related primary central nervous system lymphoma.

Primary Central Nervous System Lymphoma (PCNSL) is an aggressive brain tumour with a median survival rarely exceeding 3 months without treatment when seen in association with advanced HIV. High dose methotrexate (HD-MTX) in association with combination antiretroviral therapy (cART) is the recommended chemotherapy. However, HD-MTX may be not feasible due to poor performance status and concerns about toxicity. The 2023 guidelines from the European Association of Neuro-Oncology recommend that for people living with HIV (PLWH) presenting with PCNSL who have morbidities and/or poor functional status precluding the safe use of HD-MTX, other agents with a more favorable toxicity profile such as temozolomide might be considered. However, reports of temozolomide use for PLWH presenting PCNSL are exceedingly rare and this recommendation is extrapolated from its use in immunocompetent patients. We report here an elderly man living with HIV, with PCNSL and poor performance status who achieved long lasting remission with temozolomide plus cART. Our case illustrates the potential effectiveness of temozolomide in association with cART as first line treatment for PCNSL in a patient with poor functional status.

Diagnostic uncertainty of steroid-modified Marburg's variant of multiple sclerosis even at autopsy: A case suggesting lymphoma and related myelin loss.

MS (multiple sclerosis) has specific criteria to avoid misdiagnosis. However, the Marburg variant of MS is so fulminant that initial axonal damage and other atypical observations have been allowed in past reports. We present a 74-year-old autopsy case with a vanishing tumor after steroids and radiation therapy, which was pathologically diagnosed as a Marburg variant with initial axonal loss. The case displayed radiological lymphoma-like observations: mass effects protruding to the lateral ventricle, fused extension from the choroid plexus to white matter with C opening sign, a growing lesion from the skull dura mater, high in diffusion-weighted imaging and low in apparent diffusion coefficient on magnetic resonance imaging (MRI) suggesting high cell density lymphoma. In addition, clinical manifestations were atypical for MS: upper limb monoplegia without ipsilateral lower limb involvement, pleocytosis over 50 cells/µL, and class 3 cytological abnormality in cerebrospinal fluid. However, at autopsy following steroids and radiation therapy, there were no lymphoma-like lesions, such as mass effects, fused extensive lesions, masses on the skull dura mater, or high cell density lesions. Instead, there were only myelin losses corresponding to the MRI lesions, highlighting the potential for contamination by other diseases in steroid-modified Marburg's variant of multiple sclerosis, possibly due to lymphoma, even at autopsy.

A case report of primary central nervous system lymphoma with immune deficiency/disorder setting diagnosed by cerebrospinal fluid cytology.

Cerebrospinal fluid (CSF) cytology of primary central nervous system lymphoma arising in the immune deficiency/dysregulation setting (IDD-PCNSL) has not been described. This study presented a case of IDD-PCNSL-DLBCL, a GCB phenotype who was successfully diagnosed by CSF cytology in conjunction with ICC, ISH, FCM and clinical information.

Predicting prognosis outcomes of primary central nervous system lymphoma with high-dose methotrexate-based chemotherapeutic treatment using lipidomics.

Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy which is commonly treated with high-dose methotrexate (HD-MTX)-based chemotherapy. However, the prognosis outcome of HD-MTX-based treatment cannot be accurately predicted using the current prognostic scoring systems, such as the Memorial Sloan-Kettering Cancer Center (MSKCC) score. Methods: We studied 2 cohorts of patients with PCNSL and applied lipidomic analysis to their cerebrospinal fluid (CSF) samples. After removing the batch effects and features engineering, we applied and compared several classic machine-learning models based on lipidomic data of CSF to predict the relapse of PCNSL in patients who were treated with HD-MTX-based chemotherapy. Results: We managed to remove the batch effects and get the optimum features of each model. Finally, we found that Cox regression had the best prediction performance (AUC = 0.711) on prognosis outcomes. Conclusions: We developed a Cox regression model based on lipidomic data, which could effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.

[Relapsed primary central nervous system lymphoma treated with CD19 chimeric antigen receptor T-cell therapy and allogeneic hematopoietic stem cell transplantation].

Relapsed and/or refractory (R/R) primary central nervous system lymphoma (PCNSL) has a poor prognosis. A 57-year-old man diagnosed with PCNSL achieved a complete response by high-dose methotrexate-based chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). The disease was not cured, so he was treated with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel after the third relapse. However, the disease relapsed again 28 days after CAR T-cell therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was attempted as curative therapy after bridging with second ASCT and tirabrutinib monotherapy. Although a temporary response was achieved, the disease relapsed 98 days after allo-HSCT. While receiving tirabrutinib for relapse after allo-HSCT, the patient developed acute respiratory failure due to transplant-related toxicity and post-transplant thrombotic microangiopathy. He died 175 days after allo-HSCT. Although various treatments for PCNSL have been investigated in recent years, the treatment strategy for R/R PCNSL has not been established. Further studies are warranted to improve the outcomes of patients with R/R PCNSL.

The Baseline Pan-Immune­Inflammation Value (PIV) and PILE in Predicting Clinical Outcomes and Therapeutic Response for Primary Central Nervous System Lymphoma.

Purpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL). Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan-Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined. Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778-8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175-7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075-4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2-3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0-1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05-0.46; p < 0.001). Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.

Primary CNS Burkitt Lymphoma Presenting as Sudden Bilateral Blindness in a Patient With Underlying Kabuki Syndrome: A Case Report.

Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma (NHL). Primary CNS lymphoma (PCNSL) is a rare disease, and the subtype of Burkitt lymphoma presenting as a sole CNS lesion is an even rarer diagnosis. Acute sudden blindness is a rare presenting symptom of PCNSL or NHL in general. We present an interesting case of a four-year-old boy with dysmorphic features whose visual examination showed a sudden bilateral loss of vision. There was bilateral eye proptosis and complete ptosis. Extraocular muscles were fixed straight. The pupils were fixed and mid dilated bilaterally and there was grade 3/4 papilledema in both eyes. Neuroimaging showed a mass in the base of the skull, extending to orbits and sinuses. A cervical biopsy of the enlarged lymph nodes was taken and a histopathological diagnosis of Burkitt lymphoma was made. Genetic analysis showed a GNB1 mutation, and the patient was diagnosed with Kabuki syndrome by a pediatrician, based on characteristic dysmorphic features. Treatment with steroids and chemotherapy was initiated.

Combination of rituximab and methotrexate followed by rituximab and cytarabine in elderly patients with primary central nervous system lymphoma.

The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.

Prognostic Impacts of Age, Diagnosis Time, and Relapses in Primary CNS Lymphoma.

Background: The incidence of lymphomatous involvement of the central nervous system (CNS) has been increasing in recent years. However, the rarity of the disease has resulted in a scarcity of available data regarding its clinical presentation, natural history, and prognosis. We aimed to investigate the neurological characteristics of uncommon lymphomatous involvements confined to the CNS and to identify key variables that could serve as predictive biomarkers for treatment outcomes. Methods: We identified patients presenting with neurological symptoms and diagnosed with CNS-restricted lymphomatous involvement between 2005 and 2023. Results: We identified 44 cases, 93% of which were diagnosed with primary central nervous system lymphoma (PCNSL) and 7% with intravascular lymphoma. The median time from symptom onset to diagnosis was 47 days (range: 6-573 days), with no statistically significant difference between patients older and younger than 60 years (p = 0.22). The median follow-up time was 1144 days (range: 27-3501 days). Cognitive deterioration was the most common presenting symptom, occurring in 19 out of 44 patients (43%). Brain MRI revealed that lobar lesions were the most frequent location of lesions, found in 24 out of 44 patients (55%). By the end of the study period, 30 patients (68%) had died, with a median survival of 666 days (range: 17-3291 days). Death was significantly more common in patients who experienced relapses (p = 0.04; 95% CI: 0.99-0.03), with these patients having a four times higher chance of death (HR = 4.1; 95% CI: 1.01-16.09). The time to diagnosis significantly correlated with survival (p = 0.02; 95% CI: 0.005-0.54), as did the Eastern Cooperative Oncology Group (ECOG) performance status at the last follow-up (p = 0.006; 95% CI: 0.0012-0.62). Patients aged over 60 years did not exhibit a higher likelihood of death (p = 0.19; HR = 2.3; 95% CI: 0.63-8.61); however, the threshold age at diagnosis for the maximally predicted mortality was 64 years (ROC = 0.73; p = 0.03). Conclusions: Patients had significant delays in diagnosis, affecting patient outcomes. Cognitive deterioration and lobar lesions were prominent clinical and radiological features. Mortality was notably higher in patients with relapses and those who had a longer time to diagnosis.

[«Masks¼ of CNS demyelinating diseases. Primary lymphoma]. / «Maski¼ demieliniziruyushchikh zabolevanii TsNS. Pervichnaya limfoma.

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm that can affect the brain, eyes, and, rarely, the spinal cord. Clinical presentation and MRI findings can mimic a variety of diseases, including high-grade gliomas, infectious and granulomatous diseases, and demyelinating diseases. We describe three cases where the diagnosis of PCNSL was difficult due to an ambiguous clinical, radiological and laboratory results. The role of stereotactic biopsy remains leading in differential diagnosis; however, the invasiveness and frequent limitations of this method determine the search for additional biological markers of the disease. New evidence suggests a potential role for cerebrospinal fluid (CSF) cytokine profiles and proteomic analysis in differential diagnosis, disease progression, and treatment response.

Comparative analyses of immune cells and alpha-smooth muscle actin-positive cells under the immunological microenvironment between with and without dense fibrosis in primary central nervous system lymphoma.

Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in "stiff" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients.

Double-hit primary central nervous system lymphoma with histogenetically proven bone marrow infiltration: a case report and a review of the literature.

Double-hit lymphoma (DHL) formerly referred to high-grade B-cell lymphoma with concurrent MYC and BCL2 or BCL6 rearrangements, however, the updated 2022 World Health Organization Classification (5th edition online) excludes those with MYC and BCL 6 rearrangements from the high-grade category. DHL confined to the central nervous system (CNS), known as double-hit primary CNS lymphoma (DH-PCNSL), is rare with poorly understood clinical features. Here, we report a case of a 64-year-old man with multiple brain tumors diagnosed with DH-PCNSL who showed bone marrow (BM) infiltration early in the clinical course. The histological diagnosis was high-grade B-cell lymphoma with MYC and BCL6 rearrangements. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal accumulation except in the CNS. The patient received whole-brain radiotherapy following the failure of high-dose methotrexate. After completion of radiotherapy, the patient developed thrombocytopenia, and BM biopsy showed infiltration of DHL cells, which were not detected by repeated FDG-PET. This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.

Logistic regression modeling of cytokines for cerebrospinal fluid evaluation in primary central nervous system lymphoma.

BACKGROUND: The diagnostic utility of cerebrospinal fluid (CSF) cytology encounters impediments stemming from variability in cell collection techniques and pathologists' morphological acumen, resulting in wide-ranging CSF positivity rates for primary central nervous system lymphomas (PCNSL). Such disparity impacts patient evaluation, treatment stratagem, and prognostication. Thus, this study endeavors to explore liquid biomarkers complementary to CSF cytology or immunophenotype analysis in the diagnosis of CSF involvement. METHODS: 398 newly diagnosed PCNSL patients were categorized into CSF involvement and non-involvement groups based on CSF cytology and immunophenotype analysis. Binary logistic regression analysis was performed on 338 patients to investigate factors predicting CSF involvement and to develop a joint prediction model. An additional cohort of 60 PCNSL patients was recruited for model validation. Statistical analyses included the Mann-Whitney U test for comparing various CSF parameters between two groups. ROC curve analyses were performed for each biomarker to identify PCNSL CSF involvement. RESULTS: The cytokine IL-10 level in CSF has emerged as the most promising biomarker for CSF evaluation, boasting an ROC AUC of 0.922. C-TNFα and soluble C-IL2R demonstrate efficacy in quantifying tumor burden within the CSF. Logistic regression identified C-IL10lg (OR = 30.103, P < 0.001), C-TNC (OR = 1.126, P < 0.001), C-IL2Rlg (OR = 3.743, P = 0.029) as independent predictors for CSF involvement, contributing to a joint predictive model with an AUC of 0.935, sensitivity of 74.1 %, and specificity of 93.0 %. Validation of the model in an independent cohort confirmed its effectiveness, achieving an AUC of 0.9713. CONCLUSIONS: The identification of these feasible biomarkers and the development of an accurate prediction model may facilitate the precise evaluation of CSF status in PCNSL, offering significant advancements in patient management.