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Current Oncology (Toronto, Ont.) Jun 2023The present review aimed to establish an understanding of the pathophysiology of leptomeningeal disease as it relates to late-stage development among different cancer... (Review)
Review
The present review aimed to establish an understanding of the pathophysiology of leptomeningeal disease as it relates to late-stage development among different cancer types. For our purposes, the focused metastatic malignancies include breast cancer, lung cancer, melanoma, primary central nervous system tumors, and hematologic cancers (lymphoma, leukemia, and multiple myeloma). Of note, our discussion was limited to cancer-specific leptomeningeal metastases secondary to the aforementioned primary cancers. LMD mechanisms secondary to non-cancerous pathologies, such as infection or inflammation of the leptomeningeal layer, were excluded from our scope of review. Furthermore, we intended to characterize general leptomeningeal disease, including the specific anatomical infiltration process/area, CSF dissemination, manifesting clinical symptoms in patients afflicted with the disease, detection mechanisms, imaging modalities, and treatment therapies (both preclinical and clinical). Of these parameters, leptomeningeal disease across different primary cancers shares several features. Pathophysiology regarding the development of CNS involvement within the mentioned cancer subtypes is similar in nature and progression of disease. Consequently, detection of leptomeningeal disease, regardless of cancer type, employs several of the same techniques. Cerebrospinal fluid analysis in combination with varied imaging (CT, MRI, and PET-CT) has been noted in the current literature as the gold standard in the diagnosis of leptomeningeal metastasis. Treatment options for the disease are both varied and currently in development, given the rarity of these cases. Our review details the differences in leptomeningeal disease as they pertain through the lens of several different cancer subtypes in an effort to highlight the current state of targeted therapy, the potential shortcomings in treatment, and the direction of preclinical and clinical treatments in the future. As there is a lack of comprehensive reviews that seek to characterize leptomeningeal metastasis from various solid and hematologic cancers altogether, the authors intended to highlight not only the overlapping mechanisms but also the distinct patterning of disease detection and progression as a means to uniquely treat each metastasis type. The scarcity of LMD cases poses a barrier to more robust evaluations of this pathology. However, as treatments for primary cancers have improved over time, so has the incidence of LMD. The increase in diagnosed cases only represents a small fraction of LMD-afflicted patients. More often than not, LMD is determined upon autopsy. The motivation behind this review stems from the increased capacity to study LMD in spite of scarcity or poor patient prognosis. In vitro analysis of leptomeningeal cancer cells has allowed researchers to approach this disease at the level of cancer subtypes and markers. We ultimately hope to facilitate the clinical translation of LMD research through our discourse.
Topics: Humans; Female; Positron Emission Tomography Computed Tomography; Meningeal Carcinomatosis; Breast Neoplasms; Magnetic Resonance Imaging; Hematologic Neoplasms
PubMed: 37366925
DOI: 10.3390/curroncol30060442 -
Infection and Drug Resistance 2023Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish... (Review)
Review
Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.
PubMed: 37465179
DOI: 10.2147/IDR.S375624 -
Neurology(R) Neuroimmunology &... Nov 2023Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and...
OBJECTIVES
Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and encephalitis. In this study, we report a case of chronic enterovirus meningoencephalitis in prolonged B-cell depletion years after rituximab therapy.
METHODS
This is a case report from a German academic hospital. In addition to repeated clinical examinations, repeated brain MRI and extended CSF and laboratory diagnostics were performed. We used the CARE checklist when writing our report.
RESULTS
A 38-year-old man presented with high fever (>40°C), severe headache, and progressive neurologic and cognitive deficits. As result of previous lymphoma therapy with rituximab years ago, prolonged B-cell aplasia was detected. To restore humoral immunity, the patient received repeated infusions of immunoglobulins. In the end, a complete restitution of the physical and mental condition was achieved with the established therapy.
DISCUSSION
This case report should emphasize the importance of assessing humoral immunity even years after B-cell depletion therapy, especially in case of opportunistic infections.
Topics: Male; Humans; Adult; Rituximab; Enterovirus; Enterovirus Infections; Meningoencephalitis; B-Lymphocytes
PubMed: 37813597
DOI: 10.1212/NXI.0000000000200171 -
Japanese Journal of Radiology Aug 2023Many types of tumors can develop in the pituitary gland. In the recently revised 5th editions of the World Health Organization (WHO) classifications (2021 WHO... (Review)
Review
Many types of tumors can develop in the pituitary gland. In the recently revised 5th editions of the World Health Organization (WHO) classifications (2021 WHO Classification of Central Nervous System Tumors and the 2022 WHO Classification of Endocrine and Neuroendocrine Tumors), various changes have been made to the tumors other than pituitary neuroendocrine tumor (PitNET)/pituitary adenoma, as well as PitNET. Adamantinomatous craniopharyngioma and papillary craniopharyngioma are now considered separate tumors in the 5th edition of the WHO classification. Tumors positive for thyroid transcription factor 1, a marker of posterior pituitary cells, are now grouped together in the pituicyte tumor family in the 5th edition of the WHO classification of Endocrine and Neuroendocrine Tumors. Poorly differentiated chordoma is newly listed in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. In this paper, we present the latest WHO classification of pituitary tumors (adamantinomatous craniopharyngioma, papillary craniopharyngioma, pituitary blastoma, pituicyte tumor family, tumors of pituitary origin other than those of the pituicyte tumor family, germinoma, meningioma, chordoma, metastatic tumors, lymphoma, and pituitary incidentaloma), review diseases requiring differentiation from tumors (pituitary abscess, hypophysitis, pituitary hyperplasia, Rathke's cleft cyst, arachnoid cyst, and aneurysm), and discuss diagnoses based on imaging findings.
Topics: Humans; Pituitary Neoplasms; Craniopharyngioma; Chordoma; Pituitary Gland; Pituitary Diseases; Adenoma; Neuroendocrine Tumors; Meningeal Neoplasms; World Health Organization
PubMed: 36913010
DOI: 10.1007/s11604-023-01407-0 -
International Journal of Molecular... Dec 2023C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent...
C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent cut-off values have been defined so far mainly for neuroborreliosis. Our aim was to evaluate the value of CSF-CXCL13 as a diagnostic and treatment response marker and its role as an activity marker in a larger disease spectrum, including neuroborreliosis and other neuroinflammatory and malignant CNS-disorders. Patients who received a diagnostic lumbar puncture (LP) ( = 1234) between July 2009 and January 2023 were included in our retrospective cross-sectional study. The diagnostic performance of CSF-CXCL13 for acute neuroborreliosis was highest at a cut-off of 428.92 pg/mL (sensitivity: 92.1%; specificity: 96.5%). In addition, CXCL13 levels in CSF were significantly elevated in multiple sclerosis with clinical ( = 0.001) and radiographic disease activity ( < 0.001). The clinical utility of CSF-CXCL13 appears to be multifaceted. CSF-CXCL13 is significantly elevated in patients with neuroborreliosis and shows a rapid and sharp decline with antibiotic therapy, but it is not specific for this disease and is also highly elevated in less common subacute neuroinfectious diseases, such as neurosyphilis and cryptococcal meningitis or in primary/secondary B-cell lymphoma.
Topics: Humans; Cross-Sectional Studies; Retrospective Studies; Spinal Puncture; Multiple Sclerosis; Neurosyphilis; Syndrome; Chemokine CXCL13
PubMed: 38203597
DOI: 10.3390/ijms25010425 -
BioRxiv : the Preprint Server For... Dec 2023Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor...
Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes.
PubMed: 38187773
DOI: 10.1101/2023.12.18.572239 -
Annals of Medicine and Surgery (2012) Oct 2023Cerebral lymphoma is a rare and aggressive brain tumor. It accounts for 1% of all non-Hodgkin's lymphomas (NHL) and 2% of all brain tumors. Untreated brain lymphoma has...
INTRODUCTION
Cerebral lymphoma is a rare and aggressive brain tumor. It accounts for 1% of all non-Hodgkin's lymphomas (NHL) and 2% of all brain tumors. Untreated brain lymphoma has a very poor prognosis, with an overall life expectancy of around 1.5 months.
CASE PRESENTATION
The authors report the case of a 35-year-old patient, with no previous pathological history, who presented for 3 weeks with deafness and recently aggravated otalgia. In MRI, brain imaging revealed a formation initially suggestive of an aggressive meningioma, and the histological study of the operative specimen was in favor of a diffuse large-cell non-germ-center B NHL.
CLINICAL DISCUSSION
Primary central nervous system lymphoma is an extra-nodal NHL localized to the brain, meninges, spinal cord, and eyes. In 90% of cases, these are diffuse large B-cell lymphomas, the other types being poorly characterized low-grade lymphomas, T-cell lymphomas, and Burkitt's lymphomas. MRI with gadolinium contrast is the gold standard for diagnosis which enhancement is homogeneous and well-limited, frequently associated with perilesional vascular edema. In T2-weighted sequences, there is a weak signal with restricted diffusion on diffusion-weighted imaging. The management of brain lymphoma is currently based on chemotherapy with high-dose methotrexate combined with the other agents, mainly rituximab.
CONCLUSION
Cerebral lymphoma remains a non-negligible entity of central nervous system tumors, which can be confused with several other tumors, mainly glial and meningioma.
PubMed: 37811052
DOI: 10.1097/MS9.0000000000001126 -
Clinical Case Reports Jun 2023Primary dural Hodgkin lymphoma (PDHL) is an extremely rare subset of Hodgkin lymphoma (HL). Its existence is controversial, as Hodgkin lymphoma is not traditionally...
Primary dural Hodgkin lymphoma (PDHL) is an extremely rare subset of Hodgkin lymphoma (HL). Its existence is controversial, as Hodgkin lymphoma is not traditionally thought to arise from the central nervous system (CNS) or its meninges and only 0.02% of patients with Hodgkin lymphoma have any CNS involvement. We report a case of a 71-year-old Caucasian man who presented with progressive fatigue and sudden onset slurred speech, disorientation, and memory loss. Brain imaging identified a large extra-axial right frontal mass, and he underwent urgent subtotal resection. Pathology and subsequent workup revealed Stage IAE classical Hodgkin lymphoma of the right frontal dura, with no extra-cranial disease or leptomeningeal spread detected. The patient was subsequently treated with ABVD chemotherapy (completed 2.5 of 4 planned cycles) and 36 Gy in 20 fractions of consolidative involved-site radiotherapy (ISRT). He has been followed for 5 years with no clinical or radiological signs of recurrence. This is the second confirmed case of intracranial PDHL reported in the literature, with the longest follow-up for any case of PDHL.
PubMed: 37361649
DOI: 10.1002/ccr3.7562 -
Frontiers in Pharmacology 2023Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced...
Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced aseptic meningitis is currently not reported. Herein, we present the first case of zanubrutinib-induced aseptic meningitis. A 33-year-old woman was diagnosed with relapsed/refractory follicular lymphoma and subsequently developed aseptic meningitis after receiving zanubrutinib treatment. We reviewed the literature and uncovered the lack of current reports on zanubrutinib or other BTK inhibitor-induced aseptic meningitis. Moreover, we summarized cases on aseptic meningitis induced by common chemotherapy and targeted drugs used for hematological diseases. Drug-induced aseptic meningitis (DIAM) is a drug-induced meningeal inflammation. The possible pathogenesis is the direct stimulation of the meninges via intrathecal injection of chemotherapy drugs and immune hypersensitivity response caused by immunosuppressive drugs. It is more common in women with immune deficiency and mainly manifests as persistent headache and fever. Cerebrospinal fluid examinations mainly demonstrate a significant increase in cells and proteins. DIAM diagnosis needs to exclude bacterial, fungal, viral, and tuberculosis infections; neoplastic meningitis; and systemic diseases involving the meninges. The prognosis of DIAM is usually favorable, and physicians should detect and stop the causative drug. In conclusion, zanubrutinib-induced aseptic meningitis is a rare but serious complication, and physicians should be promptly aware of this adverse event to avoid serious consequences.
PubMed: 37727390
DOI: 10.3389/fphar.2023.1242491 -
Frontiers in Veterinary Science 2023Intrathecal chemotherapy is used in human medicine for the treatment or prophylaxis of CNS hematopoietic neoplasia. However, the clinical benefits in veterinary medicine...
Intrathecal chemotherapy is used in human medicine for the treatment or prophylaxis of CNS hematopoietic neoplasia. However, the clinical benefits in veterinary medicine have been scarcely documented. A 4-year-old male entire cross-breed dog presented with a 24-h history of severe lethargy, pelvic limb weakness, and urinary retention. Examination revealed generalized peripheral lymphadenomegaly, and the neurological findings were suggestive of a myelopathy in the region of T3-L3. Following the diagnosis of multicentric lymphoblastic B-cell lymphoma (stage Vb), a modified L-LOP with cytosine arabinoside was started, and complete clinical remission was achieved. After 4 weeks, there was acute neurological deterioration (spinal pain and proprioceptive deficits) without peripheral lymphadenomegaly. MRI findings and CSF analysis were consistent with meningeal and spinal cord lymphoma infiltration at the level of L3. Intrathecal chemotherapy (cytosine arabinoside and methotrexate) were administered in the cisterna magna with systemic dexamethasone and analgesia. Clinical signs were resolved within 24 h, and the patient remained asymptomatic for 3.5 weeks. After this period, CNS relapse (proprioceptive deficits and severe thoracolumbar pain) was suspected, and repeat intrathecal chemotherapy was declined. The patient was humanely euthanized 9 weeks after the initial diagnosis. This is the first report on the clinical benefit of intrathecal chemotherapy with a combination of methotrexate and cytarabine for the management of CNS lymphoma in dogs. Based on our case, intrathecal chemotherapy with methotrexate and cytarabine can induce a short-lasting CNS clinical remission (3 weeks).
PubMed: 37732143
DOI: 10.3389/fvets.2023.1209935