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Pathology Dec 2022
Topics: Humans; Sarcoma, Myeloid; Leukemia, Promyelocytic, Acute; Meningioma; Meningeal Neoplasms
PubMed: 35249746
DOI: 10.1016/j.pathol.2021.12.291 -
BMJ Case Reports Mar 2022Cryptococcal species endocarditis is infrequently described, carries high mortality and nearly always occurs in immunocompromised states or on prosthetic valves. We...
Cryptococcal species endocarditis is infrequently described, carries high mortality and nearly always occurs in immunocompromised states or on prosthetic valves. We report the case of a man in his 70s with multiple recent hospitalisations for pneumonia, hypercalcaemia and septic tank exposure who presented with intermittent fevers, progressive weakness,and worsening encephalopathy, manifested as confusion and word-finding difficulties for 3 weeks. Workup revealed cryptococcal species on blood serum gram stain, native aortic valve endocarditis and meningitis. Cerebrospinal fluid analysis demonstrated lymphocytosis, ultimately found to be secondary to chronic lymphocytic leukaemia. Surgical valve replacement was deemed medically contraindicated and antifungal therapy was initiated. Though poorly understood with very few documented cases, management of cryptococcal endocarditis relies on prompt diagnosis, early surgery when indicated, long-term antifungal therapy and treatment of underlying immunocompromising states where possible.
Topics: Antifungal Agents; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Endocarditis; Humans; Immunocompromised Host; Meningitis; Meningitis, Cryptococcal
PubMed: 35236688
DOI: 10.1136/bcr-2021-247310 -
Laboratory Medicine Jul 2022CNS involvement is a complication in hematologic malignant neoplasms. The advantage of multiparametric flow cytometry (MFC) over conventional cytology (CC) in detecting... (Review)
Review
BACKGROUND
CNS involvement is a complication in hematologic malignant neoplasms. The advantage of multiparametric flow cytometry (MFC) over conventional cytology (CC) in detecting occult leptomeningeal disease in CSF has been proven previously, as reported in the literature. In this study, we reviewed the experience of our laboratory in evaluating CSF specimens by MFC and CC after refinement of technical procedures.
METHODS
MFC analysis was performed in 159 specimens. In 91 specimens, simultaneous CC and MFC analysis was requested and results compared.
RESULTS
Neoplastic cells were identified in 27 (17.0%) of the total samples and in 17 (18.7%) of the paired specimens group by MFC, compared with 2 (2.2%) specimens with positive results as determined by CC. MFC enabled identification of malignant cells in low-cellularity specimens (<5 cells/μL) and all neoplasm categories.
CONCLUSION
MFC allowed the detection of minimal numbers of tumor cells in CSF specimens from individuals with leukemia and lymphoma in whom CC had not been able to identify those tumor cells.
Topics: Central Nervous System Neoplasms; Cytodiagnosis; Flow Cytometry; Hematologic Diseases; Humans; Meningeal Neoplasms
PubMed: 35212763
DOI: 10.1093/labmed/lmac004 -
Central nervous system manifestations of systemic haematological malignancies and key differentials.Clinical Radiology May 2022Central nervous system (CNS) involvement by haematological malignancies is uncommon, and generally associated with a poor prognosis. Neuroimaging plays a key role in the... (Review)
Review
Central nervous system (CNS) involvement by haematological malignancies is uncommon, and generally associated with a poor prognosis. Neuroimaging plays a key role in the accurate diagnosis, including in the critical differentiation from other processes such as infection and treatment-related toxicity. This review illustrates a variety of manifestations of CNS involvement by haematological malignancies and relevant differential diagnoses. CNS involvement can be seen in lymphoma (both primary and secondary), Waldenström macroglobulinaemia, multiple myeloma, leukaemia, and the malignant histiocytoses. The typical patterns vary between the different disorders, for example, in the most common sites of involvement and the relative frequency of parenchymal and meningeal involvement. Adjacent structures may also be involved. Nevertheless, there is some overlap in the imaging appearances, with common features including pre-contrast hyperdensity on computed tomography (CT), diffusion restriction, and avid post-contrast enhancement. In the post-treatment context, it is also important to distinguish between disease relapse and post-treatment effects. This includes opportunistic infections and the effects of chemotherapy and/or radiotherapy, including toxic effects and radiotherapy-induced neoplasms.
Topics: Central Nervous System; Central Nervous System Neoplasms; Hematologic Neoplasms; Humans; Lymphoma; Neuroimaging; Tomography, X-Ray Computed
PubMed: 35164931
DOI: 10.1016/j.crad.2022.01.043 -
Seminars in Ultrasound, CT, and MR Feb 2022The central nervous system (CNS) tumors constitute the most common type of solid tumors in the pediatric population. The cerebral and cerebellar parenchyma are the most... (Review)
Review
The central nervous system (CNS) tumors constitute the most common type of solid tumors in the pediatric population. The cerebral and cerebellar parenchyma are the most common site of pediatric CNS neoplasms. Imaging plays an important role in detection, characterization, staging and prognostication of brain tumors. The focus of the current article is pediatric brain tumor imaging with emphasis on pearls and pitfalls of conventional and advanced imaging in various pediatric brain tumor subtypes. The article also elucidates changes in brain tumor terms and entities as applicable to pediatric patients, updated as per World Health Organization (WHO) 2016 classification of primary CNS tumors. This classification introduced the genetic and/or molecular information of primary CNS neoplasms as part of comprehensive tumor pathology report in the routine clinical workflow. The concepts from 2016 classification have been further refined based on current research, by the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) group and published in the form of updates. The updates serve as guidelines in the time interval between WHO updates and expect to be broadly adopted in the subsequent WHO classification. The current review covers most pediatric brain tumors except pituitary tumors, meningeal origin tumors, nerve sheath tumors and CNS lymphoma/leukemia.
Topics: Brain Neoplasms; Central Nervous System Neoplasms; Child; Diagnostic Imaging; Humans; World Health Organization
PubMed: 35164908
DOI: 10.1053/j.sult.2021.05.004 -
Cell Reports. Medicine Dec 2021Acute lymphoblastic leukemia (ALL) dissemination to the central nervous system (CNS) is a challenging clinical problem whose underlying mechanisms are poorly understood....
Acute lymphoblastic leukemia (ALL) dissemination to the central nervous system (CNS) is a challenging clinical problem whose underlying mechanisms are poorly understood. Here, we show that primary human ALL samples injected into the femora of immunodeficient mice migrate to the skull and vertebral bone marrow and provoke bone lesions that enable passage into the subarachnoid space. Treatment of leukemia xenografted mice with a biologic antagonist of receptor activator of nuclear factor κB ligand (RANKL) blocks this entry route. In addition to erosion of cranial and vertebral bone, samples from individuals with B-ALL also penetrate the blood-cerebrospinal fluid barrier of recipient mice. Co-administration of C-X-C chemokine receptor 4 (CXCR4) and RANKL antagonists attenuate both identified routes of entry. Our findings suggest that targeted RANKL and CXCR4 pathway inhibitors could attenuate routes of leukemia blast CNS invasion and provide benefit for B-ALL-affected individuals.
Topics: Animals; Blast Crisis; Cell Line, Tumor; Central Nervous System; Fusion Proteins, bcr-abl; Gene Rearrangement; Histone-Lysine N-Methyltransferase; Humans; Mice, Inbred NOD; Models, Biological; Myeloid-Lymphoid Leukemia Protein; Neoplasm Invasiveness; Osteoprotegerin; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; RANK Ligand; Receptors, CXCR4; Spine; Subarachnoid Space; Xenograft Model Antitumor Assays; Mice
PubMed: 35028611
DOI: 10.1016/j.xcrm.2021.100470 -
Blood Cancer Discovery Jan 2022Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed...
Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease. SIGNIFICANCE: Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition..
Topics: Central Nervous System; Central Nervous System Diseases; Central Nervous System Neoplasms; Humans; Meningeal Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Biosynthesis; Proteomics
PubMed: 35019858
DOI: 10.1158/2643-3230.BCD-20-0216 -
Frontiers in Cell and Developmental... 2021Involvement of the Central Nervous System (CNS) in acute leukemia confers poor prognosis and lower overall survival. Existing CNS-directed therapies are associated with... (Review)
Review
Involvement of the Central Nervous System (CNS) in acute leukemia confers poor prognosis and lower overall survival. Existing CNS-directed therapies are associated with a significant risk of short- or long-term toxicities. Leukemic cells can metabolically adapt and survive in the microenvironment of the CNS. The supporting role of the CNS microenvironment in leukemia progression and dissemination has not received sufficient attention. Understanding the mechanism by which leukemic cells survive in the nutrient-poor and oxygen-deprived CNS microenvironment will lead to the development of more specific and less toxic therapies. Here, we review the current literature regarding the roles of metabolic reprogramming in leukemic cell adhesion and survival in the CNS.
PubMed: 34957100
DOI: 10.3389/fcell.2021.767510 -
Parasitology International Apr 2022The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes eosinophilic meningitis or...
The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes eosinophilic meningitis or meningoencephalitis. Heme oxygenase 1 (HO-1) has several cytoprotective properties such as anti-oxidative, anti-inflammatory, and anti-apoptotic effects. HO-1 in brain tissues was induced in A. cantonensis-infected group and showed positive modulation in cobalt protoporphyrin (CoPP)-treated groups. Assay methods for the therapeutic effect include western blot analysis, enzyme-linked immunosorbent assay, gelatin zymography, blood-brain barrier permeability evaluation and eosinophil count in cerebrospinal fluid. The combination of albendazole (ABZ) and CoPP significantly decreased pro-inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-5, and IL-33 but significantly increased anti-inflammatory cytokines IL-10 and transforming growth factor-β. In addition, worm recovery, matrix metalloproteinase-9, BBB permeability, and eosinophil counts were decreased in the ABZ and CoPP co-treated groups. Induction of HO-1 with CoPP strongly inhibited the protein levels of caspase-3 and increased the induction of annexin-V and B-cell leukemia 2. Thus, co-treatment with ABZ and CoPP prevented A. cantonensis-induced eosinophilic meningoencephalitis and its anti-apoptotic effect by promoting HO-1 signaling prior to BBB dysfunction. HO-1 induction might be a therapeutic modality for eosinophilic meningoencephalitis.
Topics: Albendazole; Angiostrongylus cantonensis; Animals; Anti-Inflammatory Agents; Apoptosis; Cytokines; Encephalitis; Heme Oxygenase-1; Male; Meningoencephalitis; Mice; Mice, Inbred BALB C; Strongylida Infections
PubMed: 34942361
DOI: 10.1016/j.parint.2021.102528 -
Scientific Reports Dec 2021Central nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia. In prior work we found that the...
Central nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia. In prior work we found that the meninges, the thin layer of tissue that covers the brain and spinal cord, harbor leukemia cells in the CNS. Importantly, direct interactions between leukemia and meningeal cells enabled leukemia chemoresistance. Herein, we show that an antibody targeting CD99, a transmembrane protein expressed on meningeal cells and many leukemia cells, disrupts adhesion between leukemia and meningeal cells and restores sensitivity of the leukemia cells to chemotherapy. This work identifies a mechanism regulating critical intercellular interactions within the CNS leukemia niche and may lead to novel therapeutic approaches for overcoming niche-mediated chemoresistance.
Topics: 12E7 Antigen; Antibodies, Monoclonal; Drug Resistance, Neoplasm; Humans; Meningeal Neoplasms; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured
PubMed: 34934147
DOI: 10.1038/s41598-021-03929-x