A case of primary angiitis of the central nervous system diagnosed and treated based on HR-MRI

Objective:To summarize the clinical features,imaging manifestations,therapeutic options,and prognosis of the primary angiitis of the central nervous system(PACNS)and to explore the role of high-resolution magnetic resonance imaging(HR-MRI)in the PACNS diagnosis and treatment.Methods:One patient with PACNS treated by HR-MRI was retrospectively analyzed and summarized by combining relevant literature.Results:The patient was a young female who was hospitalized with progressive cerebral infarction and multiple intracranial arterial stenosis.HR-MRI indicated vasculitic changes.After excluding other diseases,hormone shock combined with immunosuppression was given,followed by long-term rehabilitation treatment.The patient’s condition tended to stabilize,and the prognosis was satisfactory.Conclusion PACNS is challenging to diagnose and is characterized by poor prognosis and easy recurrence.HR-MRI plays an important role in the clinical diagnosis and treatment adjustment for PACNS.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Distinctive magnetic resonance imaging features in primary central nervous system lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a rare malignant tumor originating from the lymphatic hematopoietic system.It exhibits unique imaging manifestations due to its biological characteristics.CASE SUMMARY Magnetic resonance imaging(MRI)with diffusion-weighted imaging(DWI),perfusion-weighted imaging(PWI),and magnetic resonance spectroscopy was performed.The imaging findings showed multiple space-occupying lesions with low signal on T1-weighted imaging,uniform high signal on T2-weighted imaging,and obvious enhancement on contrast-enhanced scans.DWI revealed diffusion restriction,PWI demonstrated hypoperfusion,and spectroscopy showed elevated choline peak and decreased N-acetylaspartic acid.The patient's condition significantly improved after hormone shock therapy.CONCLUSION This case highlights the distinctive imaging features of PCNSL and their importance in accurate diagnosis and management.

B-scan ultrasound and cytology of the vitreous in primary central nervous system lymphoma with vitreoretinal involvement

AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma(VRL) and primary central nervous system lymphoma(PCNSL).METHODS: The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin(IL)-10 and IL-6.RESULTS: Twenty-six eyes(19.4%) out of 134 eyes of 67 patients(47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes(10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes(17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant.CONCLUSION: A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.

Imaging of hemorrhagic primary central nervous system lymphoma: A case report

BACKGROUND A primary central nervous system lymphoma(PCNSL)presenting with massive hemorrhage is a rare occurrence that is difficult to distinguish from a high-grade glioblastoma.Comprehensive descriptions of the imaging characteristics of such tumors have not yet been reported.Herein,we reported a case of a PCNSL with massive hemorrhage by presenting the imaging features of computed tomography(CT)imaging and structural and perfusion magnetic resonance imaging(MRI).CASE SUMMARY A 48-year-old man presented with headache lasting for 10 d.CT of the brain showed a round,heterogeneous,high-density lesion with surrounding edema in the right temporal lobe.For further diagnosis,a series of MRI examinations of the brain were subsequently performed,and a hemorrhagic lesion with ring-like enhancement was determined.The whole lesion was relatively hypoperfused on arterial spin labeling images.Surgical resection of the lesion and histopathological examination confirmed that the lesion was a diffuse large B-cell lymphoma with massive hemorrhage.CONCLUSION PCNSLs with hemorrhage occur very rarely,and structural and perfusion MRI examinations are requested exceedingly rarely.This case provided insight into some characteristics of a hemorrhagic lymphoma on CT and MRI examinations.Perfusion MRI examination may be useful for the differential diagnosis of PCNSLs and other brain tumors.

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial

Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary central nervous system lymphoma(PCNSL).Methods:A prospective,single-center phase II clinical trial was conducted.Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied.The R-FPD regimen consisted of rituximab(375 mg/m2 i.v.on D0),fotemustine(100 mg/m2 i.v.on D1),pemetrexed(600 mg/m2 i.v.on D1),and dexamethasone(40 mg i.v.on D1-5).Patients 60 years or younger who showed a complete response(CR)were treated with 23.4 Gy of WBRT after the end of chemotherapy;those older than 60 years with CR were treated with a wait-and-see approach;and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy+local tumor field irradiation up to 45 Gy,regardless of age.Results:A total of 30 patients were included.After 2 cycles,the objective response rate(ORR)was 96.5%(28/29,1 CR,27 PR,0 SD,and 1 PD).After 4 cycles,the ORR was 73.1%(19/26,11 CR,8 PR,4 SD,and 3 PD).After WBRT,the ORR was 90.9%(10/11,7 CR,3 PR,and 1 SD).The grade III and IV toxicity responses were mainly leukopenia(20.0%),thrombocytopenia(23.3%),and anemia(10.0%).Conclusions:Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

Temozolomide plus rituximab in the treatment of recurrent central nervous system lymphoma:Case report and literature review

Objective： The aim of our study was to investigate the treatment of recurrent central nervous system lymphoma. Methods： A case of recurrent central nervous system lymphoma in a 46-year-old male was treated with temozolomide 150 mg/m2 per day for 5 days; rituximab 750 mg/m2 on dl and d8, injected from Ommaya capsule to lateral ventricle, cycles were repeated every 28 days. Results： The patient achieved complete remission and the side effects was light after the treatment. Conclusion： Using this therapy method had certain curative effect on recurrent central nervous system lymphoma. Further studies should be needed on its indication.

Primary isolated central nervous system acute lymphoblastic leukemia with BCR-ABL1 rearrangement:A case report

BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration.It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement.CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis,with no involvement in peripheral blood or bone marrow.Identification of abnormal phenotypes of blast cells,and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia.The patient received a combination of intrathecal therapy and high-dose chemotherapy.But the benefits of the treatments were short-lived and she experienced recurrence.CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy.New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.

Primary central nervous system lymphoma presenting as a single choroidal lesion mimicking metastasis:A case report

BACKGROUND Primary choroidal lymphoma is usually an indolent B-cell lymphoma and rarely progresses to extraocular sites.Herein,we report a case of primary choroidal lymphoma diagnosed as diffuse large B-cell lymphoma(DLBL),which progressed to the brain parenchyma after 4 mo.CASE SUMMARY A 78-year-old man presented with diminution of vision in his right eye.A choroidal lesion suspected of metastatic lesion was observed in the right eye by ophthalmologic examination.To discover the primary tumor,imaging investigations were performed but no malignant lesion was detected.After 4 mo,the patient returned to the clinic presenting with neurological symptoms.Brain magnetic resonance imaging revealed an abnormal contrast-enhancing mass in the left cerebellum.A stereotactic biopsy was performed,and DLBL was confirmed.The patient received the high dose methotrexate-based chemotherapy and he achieved complete remission.CONCLUSION Primary choroidal lymphoma is usually known to have a benign clinical course without systemic involvement.We present a rare case of primary choroidal lymphoma diagnosed as DLBL that progressed to the brain parenchyma within months.

Diffuse Large B-Cell Lymphoma of the Central Nervous System. Immunophenotype, Clinicopathological Features and Differential Diagnosis

Background: Diffuse large B-cell lymphomas of the central nervous system (DLBCL CNS) represent less than 1% of all lymphomas and between 2% and 3% of all cerebral tumors. They occur in adults of 60 years of age or more. The objective of this work is to describe the clinical-pathological characteristics, the immunophenotype and the differential diagnosis. Clinical Case: From the files of the surgical pathology unit we found four cases of primary diffuse large B cell lymphoma of the central nervous system in a 6-year period. Three corresponded to women over 47 years of age and the other to a 42-year-old man. The time of evolution was between 2 and 4 months. The symptoms were headache, blurred vision, hemiparesis, and seizures. Localization was in the pineal region, the frontal, parietal regions, and the right thalamus. Morphologically, large lymphoid cells with a diffuse growth pattern and necrosis were observed. Immunohistochemical markers, such as CD 20 and bcl2 were positive, one was positive to CD3. Expression of bcl6 and CD 10 was positive in one case, and MUM-1 was positive in three cases. All the cases were negative for Epstein-Barr virus. Conclusions: The diffuse large-B cell lymphoma of the central nervous system is rare. Its average age of presentation is at 60 years or older. The localization is in the pineal, frontal, parietal and thalamic regions. Three cases were originated by activated B lymphocyte (MUM-1 expression) and other from the Germinal Center (GC) (CD 10 expression). The clinical course was bad. The four patients died shortly after the diagnosis.

Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients

Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also analyzed.Structural variations were identified in all patients with a mean of 349,which did not significantly influence prognosis.Copy loss occurred in all samples,while gains were detected in 77.9%of the samples.The high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the cases.CD79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.

Primary angiitis of the central nervous system： a case report

Primary angiitis of the central nervous system is a rare and difficult entity. Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis. The 50-year-old male had a fluctuating disease course for more than 3 years. He presented visual disorders, seizure, cognitive impairment, hypersomnia, unsteady gait, dysphasia, dysphagia, and incontinence. Magnetic resonance imaging showed multiple, supratentorial and infratentorial abnormal signals, while cerebrospinal fluid and cerebral angiography were normal. Magnetic resonance spectrum showed a decrease of N-acetyl-aspartate. Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis, cicatrization, demyelination and focal hemorrhages.

A 5-year-old child presenting with tumor-like primary angiitis of the central nervous system

Introduction:Primary angiitis of the central nervous system(PACNS)is a vasculitis confined to the CNS.A small proportion of the lesions may present as a tumor-like mass,which is rarely seen in children.Case presentation:A 5-year-old girl was admitted to our hospital because of an intermittent headache.Brain imaging suggested a space-occupying lesion in the right cerebral hemisphere.The final diagnosis was PACNS with a lymphocytic pattern by stereotactic brain biopsy.Her condition improved after immunotherapy.Conclusion:Pediatricians should consider the possibility of PACNS when encountering intracranial tumor-like lesions.Early diagnosis of tumor-like PACNS and prompt immunotherapy could improve the long-term prognosis and avoid surgery.

Advances in Pathobiology of Primary Central Nervous System Lymphoma

Objective： Primary central nervous system lymphoma （PCNSL） is a specific type ofnon-Hodgkin lymphoma with poor prognosis. The rare incidence of this disease and difficulty to obtain sufficient tissue material impede deep research into PCNSL. However, application of modern molecular techniques makes it possible to find biological characteristics exclusive to PCNSL. Therefore, we systematically reviewed the latest research progress on biological characteristics and pathogenesis of PCNSL. Data Sources： The data analyzed in this review were from the articles listed in PubMed database. Study Selection： Articles focusing on the biology of PCNSL at the cytogenetic or molecular level were reviewed, including clinical, basic research, and review articles. Results： With respect to histopathology, perivascular growth pattern and reactive perivascular T-cell infiltration are regarded as typical histopathological manifestations of tumor cells in PCNSL. Moreover, tumor cells of PCNSL predominantly express an activated B-cell-like phenotype, including CD10- BCL-6＋ MUM1＋, CD10- BCL-6 MUM 1＋, and CD10 BCL-6 MUM 1- . On the molecular level, some molecular and genetic alterations may contribute to malignant transformation, including mutations of proto-oncogenes and tumor suppressor genes, gains and losses of genetic material, as well as aberrant activation of some important signaling pathways, such as nuclear factor-κB and JAK/STAT pathway. Conclusions： The integrated molecular mechanisms involved in pathogenesis of PCNSL are not well understood. The important biomarkers indicating prognosis are not identified. Multicenter studies should be carried out to elucidate pathogenesis of PCNSL to find novel and effective therapeutic strategies.

agnetic Resonance Imaging Characteristics of Primary Central Nervous System T-cell Lymphoma

Primary central nervous system lymphomas （PCNSLs） are rare non-Hodgkin tumors defined as lymphomas of the central nervous system （CNS） without primary tumor elsewhere. It was reported that PCNSLs represented only 3-7% of primary brain tumors and 1-5% of all lymphomas. Most of PCNSLs are B-cell lymphomas, while T-cell PCNSL （T-PCNSL） is extremely rare, the majority of the reported T-PCNSL cases are clinically sporadic that focus on the treatment, and its imaging features have rarely been described. Herein, we report a case of T-PCNSL and comprehensively summarize its magnetic resonance imaging （MRI） characteristics. It is the first time in China to locus on the MRI diagnosis of T-PCNSL.

Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma

Background Clinical outcome in patients with primary central nervous lymphoma （PCNSL） is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL. Methods One hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxpl, and LMO2 were performed. All cases were followed-up regularly. Results The common sites of involvement were frontal lobe （54.8%） and thalamus （16.5%）. Diffuse large B-cell lymphoma composed of 96.5% of the cases. The median overall survival was 22 （4-41） months, and the 5-year survival rate was 22.8%. Age 〉65 years, serum globulin 〉40 g/L, large size of tumor, lymphocyte count ≥1×10^9/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxpl, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size, and high serum globulin were independent prognostic factors for PCNSL. Conclusions PCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.

A Case of Primary Central Nervous System Lymphoma with Ciliary Body Involvement

INTRODUCTION Primary central nervous system lymphoma （PCNSL） is defined as lymphoma confined to the brain, eye, spinal cord, or leptomeninges. It constitutes approximately 3% of all brain tumors, and 2-3% of all cases of non-Hodgkin lymphoma. Ocular involvement can be detected during clinical staging in about 20% of patients with PCNSL, with primary vitreous retinal lymphoma being the most common subtype. Uveal involvement of PCNSL is uncommon, and PCNSL with ciliary body involvement （CBL）, to the best of our knowledge, has not been reported.