Pathology of primary central nervous system lymphoma

✓ The understanding of primary central nervous system lymphoma (PCNSL) has lagged behind that of the much more common systemic, nodal lymphomas. Reasons for this include the relative rarity of PCNSL and the fact that these lesions differ in some ways from their histologically similar systemic counterparts. The purpose of this paper is twofold: first, the author provides concise descriptions of the pathological features of both common and uncommon types of PCNSL while discussing issues such as the confusion surrounding histological classification of PCNSLs, problems related to intraoperative diagnosis, and the appropriate diagnostic work up. Second, the author discusses a small number of molecular studies to demonstrate the great promise they offer. Such studies have already clarified some issues, including the category of lymphocyte from which the majority of PCNSLs are derived. Hopefully in the future these studies will help guide treatment decisions.

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Primary leptomeningeal lymphoma masquerading as infectious tubercular meningitis

BMJ Case Reports ◽

10.1136/bcr-2021-243574 ◽

2021 ◽

Vol 14 (9) ◽

pp. e243574

Author(s):

Salini Sumangala ◽

Thidar Htwe ◽

Yousuf Ansari ◽

Lidia Martinez- Alvarez

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Correct Diagnosis ◽

Central Nervous System Lymphoma ◽

Final Diagnosis ◽

Csf Analysis ◽

Antitubercular Treatment ◽

Lymphoma Treatment ◽

Work Up ◽

Timely Treatment

Primary central nervous system lymphoma (PCNSL) is infrequent and often poses diagnostic conundrums due to its protean manifestations. We present the case of a South Asian young man presenting with raised intracranial pressure and a lymphocytic cerebrospinal fluid (CSF) with pronounced hypoglycorrhachia. Progression of the neuro-ophthalmic signs while on early stages of antitubercular treatment led to additional investigations that produced a final diagnosis of primary leptomeningeal lymphoma. Treatment with chemoimmunotherapy (methotrexate, cytarabine, thiotepa and rituximab (MATRix)) achieved full radiological remission followed by successful autologous transplant. This case highlights the difficulties and diagnostic dilemmas when PCNSL presents as a chronic meningeal infiltrative process. While contextually this CSF is most often indicative of central nervous system tuberculosis and justifies empirical treatment initiation alone, it is essential to include differential diagnoses in the investigation work-up, which also carry poor prognosis without timely treatment. High suspicion, multidisciplinary collaboration and appropriate CSF analysis were the key for a correct diagnosis.

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Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

10.1101/2020.04.18.20065805 ◽

2020 ◽

Author(s):

Haoyu Ruan ◽

Zhe Wang ◽

Yue Zhai ◽

Ying Xu ◽

Linyu Pi ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

B Cells ◽

B Cell ◽

Single Cell ◽

Central Nervous System Lymphoma ◽

B Cell Lymphoma ◽

Great Promise ◽

Leptomeningeal Involvement

AbstractDiffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

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Nanomedicine Applications in Treatment of Primary Central Nervous System Lymphoma: Current State of the Art

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3133 ◽

2021 ◽

Vol 17 (8) ◽

pp. 1459-1485

Author(s):

Mengyao Wang ◽

Ying Qu ◽

Danrong Hu ◽

Ting Niu ◽

Zhiyong Qian

Keyword(s):

Drug Delivery ◽

Central Nervous System ◽

Nervous System ◽

Drug Delivery Systems ◽

Central Nervous System Lymphoma ◽

Delivery Systems ◽

Brain Diseases ◽

Current Status ◽

Great Promise ◽

Antitumor Effects

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive subtype of extra nodal non-Hodgkin lymphoma (NHL), which is confined in the central nervous system (CNS). Despite recent advancements in treatment options, the overall prognosis of PCNSL remains poor. Among many unfavorable factors affecting efficacy, inadequate drug delivery into the CNS is still the thorniest challenge. Blood-brain barrier (BBB) constitutes a significant impediment, restricting entry of most therapeutics to the brain. Nanotechnology has offered great promise for brain diseases, as various nano-based drug delivery systems (NDDSs) have been developed for delivery of theranostic agents in to the CNS. These drug delivery systems possess significant advantages, including good feasibility, reliable safety profile, excellent BBB penetration and potent antitumor effects. As for treatment of PCNSL, numerous well-developed BBB-crossing nano-based strategies can be applied with proper modifications and improvements. Some exquisitely designed NDDSs specific for PCNSL have shown great potential. In this review, we provide a summary on current status of diagnosis and treatment of PCNSL, followed by an overview of BBB-crossing strategies applied in management of PCNSL, both novel and wellestablished. Finally, challenges and future perspectives in this field are also discussed.

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