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PubMed - Rare Brain Tumor (99 unread)

Author Correction: Federated learning enables big data for rare cancer boundary detection

Fetched: January 27th, 2023, 5:01am GMT by Sarthak Pati

Nat Commun. 2023 Jan 26;14(1):436. doi: 10.1038/s41467-023-36188-7.

NO ABSTRACT

PMID:36702828 | DOI:10.1038/s41467-023-36188-7

Epstein-Barr virus-associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case

Fetched: January 25th, 2023, 5:01am GMT by Joanna K Tabor

J Neurosurg Case Lessons. 2023 Jan 23;5(4):CASE22532. doi: 10.3171/CASE22532. Print 2023 Jan 23.

ABSTRACT

BACKGROUND: Primary intracranial leiomyosarcomas (PILMSs) are extremely rare tumors arising from smooth muscle connective tissue. PILMSs have been shown to be associated with Epstein-Barr virus (EBV). Thus far, EBV-associated PILMS has been exclusively described in immunocompromised patients.

OBSERVATIONS: A 40-year-old male presented with a 2-year history of left-sided headaches, nausea, and vomiting. Magnetic resonance imaging demonstrated a large, heterogeneously enhancing, lobulated, dura-based mass arising from the left middle cranial fossa with associated edema and mass effect. The patient underwent an uncomplicated resection of suspected meningioma; neuropathology revealed the exceedingly rare diagnosis of EBV-associated PILMS. Follow-up testing for human immunodeficiency virus (HIV) and other immunodeficiencies confirmed the patient's immunocompetent status.

LESSONS: Primary intracranial smooth muscle tumors are often misdiagnosed as meningiomas due to their similar appearance on imaging. PILMSs have a poor prognosis and gross total resection is the mainstay of treatment in the absence of clear recommendations for management. Prompt diagnosis and resection are important; therefore, these tumors should be included in the differential of dura-based tumors, especially among immunocompromised patients. Although EBV-associated PILMSs usually occur in immunocompromised individuals, their presence cannot be ruled out in immunocompetent patients.

PMID:36692065 | DOI:10.3171/CASE22532

Permalink for 'Neurofeedback Treatment Affects Affective Symptoms, But Not Perceived Cognitive Impairment in Cancer Patients: Results of an Explorative Randomized Controlled Trial'

Neurofeedback Treatment Affects Affective Symptoms, But Not Perceived Cognitive Impairment in Cancer Patients: Results of an Explorative Randomized Controlled Trial

Fetched: January 25th, 2023, 5:01am GMT by Madeleine Fink

Integr Cancer Ther. 2023 Jan-Dec;22:15347354221149950. doi: 10.1177/15347354221149950.

ABSTRACT

BACKGROUND: EEG biofeedback (NF) is an established therapy to enable individuals to influence their own cognitive-emotional state by addressing changes in brainwaves. Psycho-oncological approaches of NF in cancer patients are rare and effects are hardly studied.

OBJECTIVE: The aim of this explorative, randomized controlled trial was to test the effectiveness of an alpha and theta NF training protocol, compared to mindfulness based therapy as an established psycho-oncological treatment.

METHODS: Of initially 62 screened patients, 56 were included (inclusion criteria were cancer independent of tumor stage, age >18 years, German speaking; exclusion criteria suicidal ideation, brain tumor). Randomization and stratification (tumor stage) was conducted by a computer system. Participants got 10 sessions over 5 weeks, in (a) an NF intervention (n = 21; 13 female, 8 male; MAge = 52.95(10 519); range = 31 to 73 years)) or (b) a mindfulness group therapy as control condition (CG; n = 21; ie, 15 female, 6 male; MAge = 50.33(8708); range = 32 to 67 years)). Outcome parameters included self-reported cognitive impairment (PCI) as primary outcome, and secondary outcomes of emotional distress (DT, PHQ-8, GAD-7), fatigue (MFI-20), rumination (RSQ), quality of life (QoL, EORTC-30 QoL), self-efficacy (GSE), and changes in EEG alpha, and theta-beta band performance in the NF condition.

RESULTS: No changes in cognitive impairment were found (P = .079), neither in NF nor CG. High affective distress was evident, with 70.7% showing elevated distress and 34.1% showing severe depressive symptoms. Affective symptoms of distress (P ≤ .01), depression (P ≤ .05) and generalized anxiety (P ≤ .05) decreased significantly over time. No differences between NF and CG were found. There was a significant increase of the alpha band (P ≤ .05; N = 15) over the NF sessions. Self-efficacy predicted QoL increase in NF with P ≤ .001 and an explained variance of 48.2%.

CONCLUSION: This is the first study to investigate NF technique with regard to basic mechanisms of effectiveness in a sample of cancer patients, compared to an established psycho-oncological intervention in this field. Though there were no changes in cognitive impairment, present data show that NF improves affective symptoms comparably to mindfulness-based therapy and even more pronounced in QoL and self-efficacy.Trial registration: ID: DRKS00015773.

PMID:36691908 | DOI:10.1177/15347354221149950

Permalink for 'Neuroprotective Effects and Metabolomics Study of Protopanaxatriol (PPT) on Cerebral Ischemia/Reperfusion Injury In Vitro and In Vivo'

Neuroprotective Effects and Metabolomics Study of Protopanaxatriol (PPT) on Cerebral Ischemia/Reperfusion Injury In Vitro and In Vivo

Fetched: January 25th, 2023, 5:01am GMT by Fulin Wu

Int J Mol Sci. 2023 Jan 16;24(2):1789. doi: 10.3390/ijms24021789.

ABSTRACT

Stroke, one of the leading causes of disability and death worldwide, is a severe neurological disease that threatens human life. Protopanaxatriol (PPT), panaxatriol-type saponin aglycone, is a rare saponin that exists in Panax ginseng and Panax Noto-ginseng. In this study, we established an oxygen-glucose deprivation (OGD)-PC12 cell model and middle cerebral artery occlusion/reperfusion (MCAO/R) model to evaluate the neuroprotective effects of PPT in vitro and in vivo. In addition, metabolomics analysis was performed on rat plasma and brain tissue samples to find relevant biomarkers and metabolic pathways. The results showed that PPT could significantly regulate the levels of LDH, MDA, SOD, TNF-α and IL-6 factors in OGD-PC12 cells in vitro. PPT can reduce the neurological deficit score and infarct volume of brain tissue in rats, restore the integrity of the blood-brain barrier, reduce pathological damage, and regulate TNF-α, IL-1β, IL-6, MDA, and SOD factors. In addition, the results of metabolomics found that PPT can regulate 19 biomarkers involving five metabolic pathways, including amino acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. Thus, it could be inferred that PPT might serve as a novel natural agent for MCAO/R treatment.

PMID:36675303 | PMC:PMC9861888 | DOI:10.3390/ijms24021789

Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma

Fetched: January 25th, 2023, 5:01am GMT by Wajd N Al-Holou

Neoplasia. 2023 Feb;36:100872. doi: 10.1016/j.neo.2022.100872. Epub 2023 Jan 6.

ABSTRACT

PURPOSE: Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities.

EXPERIMENTAL DESIGN: We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs.

RESULTS: These studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurrence. Analyses of clinical databases revealed significant association of this transcriptional profile with worse overall survival and upregulation at recurrence. Notably, gene expression analyses identified upregulation of TGFβ signaling, and more than one-hundred-fold increase in THY1 levels at recurrence. Furthermore, THY1-positive cells represented <10% of cells in treatment-naïve tumors, compared to 75-96% in recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples and determined that they were inherently resistant to chemoradiation in orthotopic models. Additionally, using image-guided biopsies from treatment-naïve human GBM, we conducted spatial transcriptomic analyses. This revealed rare THY1+ regions characterized by mesenchymal/stem-like gene expression, analogous to our recurrent mouse model, which co-localized with macrophages within the perivascular niche. We then inhibited TGFBRI activity in vivo which decreased mesenchymal/stem-like protein levels, including THY1, and restored sensitivity to TMZ/IR in recurrent tumors.

CONCLUSIONS: These findings reveal that GBM recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive, mesenchymal cells within the perivascular niche.

PMID:36621024 | PMC:PMC9841165 | DOI:10.1016/j.neo.2022.100872

Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study

Fetched: January 24th, 2023, 5:01am GMT by Aymeric Amelot

Neurology. 2023 Jan 23:10.1212/WNL.0000000000206834. doi: 10.1212/WNL.0000000000206834. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Primary spinal glioblastoma is extremely rare. The dramatic neurological deterioration and unresectability of primary spinal glioblastoma makes it a particularly disabling malignant neoplasm. Since it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited.

METHODS: Primary spinal glioblastomas were identified from The French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age ≥ 18 years at diagnosis, spinal location, histopathological diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathological review. The primary outcome was overall survival. Therapeutic interventions and neurological outcomes were also collected.

RESULTS: Thirty-three patients with an histopathologically confirmed primary spinal glioblastoma (median age 50.9 years) were included (27 centers). The median overall survival (OS) was 13.1 months (range 2.5-23.7) and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, ECOG PS at 0-1 was the only independent predictor of longer OS [Hazard Ratio: 0.13, 95%CI 0.02-0.801; p=0.02], whereas a Karnofsky PS score <60 [Hazard Ratio: 2.89, 95%CI 1.05-7.92; p=0.03] and a cervical anatomical location [Hazard Ratio: 4.14, 95%CI 1.32-12.98; p=0.01] were independent predictors of shorter OS. The ambulatory status (Frankel D-E) [Hazard Ratio: 0.38, 95%CI 0.07-1.985; p=0.250] was not an independent prognostic factor while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) [Hazard Ratio: 0.35, 95%CI 0.118-1.05; p=0.06] was at the limit of significance.

DISCUSSION: Preoperative ECOG PS, Karnofsky PS score and the location are independent predictors of overall survival of primary spinal glioblastomas in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

PMID:36690453 | DOI:10.1212/WNL.0000000000206834

Permalink for 'Genomic study and lipidomic bioassay of Leeuwenhoekiella parthenopeia: A novel rare biosphere marine bacterium that inhibits tumor cell viability'

Genomic study and lipidomic bioassay of Leeuwenhoekiella parthenopeia: A novel rare biosphere marine bacterium that inhibits tumor cell viability

Fetched: January 24th, 2023, 5:01am GMT by Giuliano Gattoni

Front Microbiol. 2023 Jan 6;13:1090197. doi: 10.3389/fmicb.2022.1090197. eCollection 2022.

ABSTRACT

The fraction of low-abundance microbiota in the marine environment is a promising target for discovering new bioactive molecules with pharmaceutical applications. Phenomena in the ocean such as diel vertical migration (DVM) and seasonal dynamic events influence the pattern of diversity of marine bacteria, conditioning the probability of isolation of uncultured bacteria. In this study, we report a new marine bacterium belonging to the rare biosphere, Leeuwenhoekiella parthenopeia sp. nov. Mr9^T, which was isolated employing seasonal and diel sampling approaches. Its complete characterization, ecology, biosynthetic gene profiling of the whole genus Leeuwenhoekiella, and bioactivity of its extract on human cells are reported. The phylogenomic and microbial diversity studies demonstrated that this bacterium is a new and rare species, barely representing 0.0029% of the bacterial community in Mediterranean Sea metagenomes. The biosynthetic profiling of species of the genus Leeuwenhoekiella showed nine functionally related gene cluster families (GCF), none were associated with pathways responsible to produce known compounds or registered patents, therefore revealing its potential to synthesize novel bioactive compounds. In vitro screenings of L. parthenopeia Mr9^T showed that the total lipid content (lipidome) of the cell membrane reduces the prostatic and brain tumor cell viability with a lower effect on normal cells. The lipidome consisted of sulfobacin A, WB 3559A, WB 3559B, docosenamide, topostin B-567, and unknown compounds. Therefore, the bioactivity could be attributed to any of these individual compounds or due to their synergistic effect. Beyond the rarity and biosynthetic potential of this bacterium, the importance and novelty of this study is the employment of sampling strategies based on ecological factors to reach the hidden microbiota, as well as the use of bacterial membrane constituents as potential novel therapeutics. Our findings open new perspectives on cultivation and the relationship between bacterial biological membrane components and their bioactivity in eukaryotic cells, encouraging similar studies in other members of the rare biosphere.

PMID:36687661 | PMC:PMC9859067 | DOI:10.3389/fmicb.2022.1090197

Case Report: Pituitary metastasis as a presenting manifestation of silent gastric cardia adenocarcinoma

Fetched: January 24th, 2023, 5:01am GMT by Andrea Ghezzi

Front Oncol. 2023 Jan 4;12:1059361. doi: 10.3389/fonc.2022.1059361. eCollection 2022.

ABSTRACT

INTRODUCTION: Pituitary metastases are very rare in cancer patients and often originate from lung or breast tumors. They usually occur in patients with known metastatic disease, but rarely may be the first presentation of the primary tumor.

METHODS: We present the case of a 58 years-old-man who reported a three-month history of polyuria-polydipsia syndrome, generalized asthenia, panhypopituitarism and bitemporal hemianopsia. Brain-MRI showed a voluminous pituitary mass causing posterior sellar enlargement and compression of the surrounding structures including pituitary stalk, optic chiasm, and optic nerves.

RESULTS: The patient underwent neurosurgical removal of the mass. Histological examination revealed a poorly differentiated adenocarcinoma of uncertain origin. A total body CT scan showed a mass in the left kidney that was subsequently removed. Histological features were consistent with a clear cell carcinoma. However, endoscopic examination of the digestive tract revealed an ulcerating and infiltrating adenocarcinoma of the gastric cardia. Total body PET/CT scan with 18F-FDG confirmed an isolated area of accumulation in the gastric cardia, with no hyperaccumulation at other sites.

CONCLUSION: To the best of our knowledge, there are no reports of pituitary metastases from gastric cardia adenocarcinoma. Our patient presented with symptoms of sellar involvement and without evidence of other body metastases. Therefore, sudden onset of diabetes insipidus and visual deterioration should lead to the suspicion of a rapidly growing pituitary mass, which may be the presenting manifestation of a primary extracranial adenocarcinoma. Histological investigation of the pituitary mass can guide the diagnostic workup, which must however be complete.

PMID:36686817 | PMC:PMC9846627 | DOI:10.3389/fonc.2022.1059361

Permalink for 'Case report: Primary intracranial mucosa-associated lymphoid tissue lymphoma presenting as two primary tumors involving the cavernous sinus and extra-axial dura, respectively'

Case report: Primary intracranial mucosa-associated lymphoid tissue lymphoma presenting as two primary tumors involving the cavernous sinus and extra-axial dura, respectively

Fetched: January 24th, 2023, 5:01am GMT by Shiyun Tian

Front Oncol. 2023 Jan 4;12:927086. doi: 10.3389/fonc.2022.927086. eCollection 2022.

ABSTRACT

Primary intracranial mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of brain tumor, with only a few reported cases worldwide that mostly have only one lesion with conventional magnetic resonance imaging (MRI) findings. Here, we present a special case of intracranial MALT lymphoma with two mass lesions radiographically consistent with meningiomas on MRI before the operation. A 66-year-old woman was admitted to the hospital with intermittent right facial pain for 1 year, aggravated for the last month. Brain MRI showed two extracerebral solid masses with similar MR signal intensity. One mass was crescent-shaped beneath the skull, and the other was in the cavernous sinus area. Lesions showed isointensity on T1WI and T2WI and an intense homogeneous enhancement after contrast agent injection. Both lesions showed hyperintensity in amide proton transfer-weighted images. The two masses were all surgically resected. The postoperative pathology indicated extranodal marginal zone B-cell lymphoma of MALT. To improve awareness of intracranial MALT lymphoma in the differential diagnosis of extra-axial lesions among clinicians, we present this report and briefly summarize previously reported cases to describe the clinical, pathological, radiological, and treatment features.

PMID:36686768 | PMC:PMC9846770 | DOI:10.3389/fonc.2022.927086

Vestibular Schwannoma Leading to Contacting Aneurysm Rupture: An Unusual Presentation

Fetched: January 24th, 2023, 5:01am GMT by Renata Marques

Cureus. 2022 Dec 19;14(12):e32716. doi: 10.7759/cureus.32716. eCollection 2022 Dec.

ABSTRACT

Subarachnoid hemorrhage (SAH) is a rare manifestation of brain tumors, being even rarer in vestibular schwannomas. We report the second case of a posterior circulation aneurysm close to the tumor capsule, responsible for SAH as an initial manifestation of a vestibular schwannoma. A 67-year-old female was admitted to the Emergency Department with sudden onset of nausea and headache. A diagnosis of a SAH and a tumor of the right cerebellopontine angle was made. An angiography showed an aneurysm in the dependency of the right anterior inferior cerebellar artery (AICA), juxtaposed to the tumor capsule. The patient underwent surgery, the tumor was removed, and the aneurysm was treated. This case highlights that SAH in patients with vestibular schwannoma may originate from a contact aneurysm. Although exceedingly rare, surgeons should consider this scenario in vestibular schwannoma presenting with SAH, and angiography is important for its diagnosis.

PMID:36686143 | PMC:PMC9850019 | DOI:10.7759/cureus.32716

Cerebral mucormycosis masquerading as brain metastasis from lung cancer: A case report

Fetched: January 24th, 2023, 5:01am GMT by Yuankun Cai

Heliyon. 2022 Dec 30;9(1):e12761. doi: 10.1016/j.heliyon.2022.e12761. eCollection 2023 Jan.

ABSTRACT

We report a rare case of concurrent pulmonary and cerebral mucormycosis initially misdiagnosed as a metastatic tumor. A 66-year-old man with a complaint of progressive right-sided limb weakness for 3 days. Head MRI showed a left parietal occupying lesion with severe edema, and a chest CT scan showed a parenchymal mass with speculation and pleural invasion in his left lung. The patient was initially diagnosed with brain metastases from lung cancer and underwent a craniotomy. Many fungal hyphae were found in the left parietal lesion, and the final pathological diagnosis of intracranial mucormycosis. After craniotomy and an entire course of treatment with liposomal amphotericin B, the patient was completely cured of both intracranial and pulmonary occupying lesions. We hope that this case experience will help expand neurosurgeons' differential diagnosis and treatment of such diseases.

PMID:36685477 | PMC:PMC9849960 | DOI:10.1016/j.heliyon.2022.e12761

A rare case of brain metastatic of primary mediastinal yolk sac tumor

Fetched: January 24th, 2023, 5:01am GMT by Cindy Cecilia

Radiol Case Rep. 2023 Jan 5;18(3):1041-1045. doi: 10.1016/j.radcr.2022.12.028. eCollection 2023 Mar.

ABSTRACT

Primary yolk sac tumors are extragonadal germ cell tumors commonly seen in children and young adults. They are more common in men. Germ cells tumor on histopathological characteristics is classified as seminoma and non-seminomatous (NSGC). The rarest form of NSGC is an extragonadal yolk sac tumor of mediastinum. Clinical presentations are not specific and may imitate other chronic disease such as other malignancies or tuberculosis such as chest discomfort, vena cava superior syndrome, fever, weight loss, and chronic cough. Immunohistochemistry showed a positive result in Alpha-fetoprotein and pan-cytokeratin. Due to its rarity, brain metastases' clinical signs and symptoms, anatomical sites, and characteristics are less well documented. However, the metastatic brain process gave similar histological findings to the primary site. Additional radiological and laboratory tests can be carried out to identify other metastatic processes. Standardized treatment of primary mediastinal sac tumors with brain metastasis has not yet been established. Combining chemotherapy, surgery and radiation treatment could improve overall outcomes and prognosis. We present a scarce case of primary mediastinal yolk sac tumor with metastatic brain process in a 32-year-old male with a short survival period.

PMID:36684631 | PMC:PMC9849995 | DOI:10.1016/j.radcr.2022.12.028

Heritable defects in telomere and mitotic function selectively predispose to sarcomas

Fetched: January 24th, 2023, 5:01am GMT by Mandy L Ballinger

Science. 2023 Jan 20;379(6629):253-260. doi: 10.1126/science.abj4784. Epub 2023 Jan 19.

ABSTRACT

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.

PMID:36656928 | DOI:10.1126/science.abj4784

Permalink for 'Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial'

Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial

Fetched: January 22nd, 2023, 5:01am GMT by Eric J Sherman

Lancet Oncol. 2023 Jan 18:S1470-2045(22)00763-X. doi: 10.1016/S1470-2045(22)00763-X. Online ahead of print.

ABSTRACT

BACKGROUND: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population.

METHODS: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m²) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m²), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete.

FINDINGS: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group).

INTERPRETATION: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated.

FUNDING: National Cancer Institute and Novartis.

PMID:36681089 | DOI:10.1016/S1470-2045(22)00763-X

Rapid ossification of a giant post-operative occipital pseudomeningocele following posterior fossa surgery

Fetched: January 22nd, 2023, 5:01am GMT by Daniel Lewis

Childs Nerv Syst. 2023 Jan 21. doi: 10.1007/s00381-023-05829-z. Online ahead of print.

ABSTRACT

Pseudomeningocele formation following posterior fossa surgery is a well-recognised complication, occurring in up to 33% of operated cases in some series. Ossification of a cranial pseudomeningocele is, however, an exceptionally rare event with only three prior reported cases. We present the unique case of a paediatric patient who developed rapid ossification of a giant occipital pseudomeningocele following posterior fossa surgery. An 8-year-old female patient underwent a midline posterior fossa craniotomy for resection of an exophytic brainstem low-grade glioma. Post-surgery, the patient developed pan-ventricular hydrocephalus and a large occipital pseudomeningocele, which initially increased in size despite a successful endoscopic third ventriculostomy (ETV) being performed. At approximately 3 months post-surgery, reduction of the pseudomeningocele was observed with associated prominent ossification of the pseudomeningocele wall on computed tomography (CT) imaging. Surgical excision was subsequently undertaken, and intra-operatively, a large ossified pseudomeningocele was found. Follow-up MRI 1 month later demonstrated almost complete resolution of the pseudomeningocele with an associated reduction in the degree of pan-ventricular ventriculomegaly. This case highlights that ossification of even giant pseudomeningoceles can occur over a time period of just a few months and clinicians should consider ossification whenever a change in size or consistency of a post-operative pseudomeningocele is encountered.

PMID:36680566 | DOI:10.1007/s00381-023-05829-z

An Update on Circular RNA in Pediatric Cancers

Fetched: January 22nd, 2023, 5:01am GMT by Angela Galardi

Biomedicines. 2022 Dec 23;11(1):36. doi: 10.3390/biomedicines11010036.

ABSTRACT

Circular RNAs (circRNAs) are a class of single-stranded closed noncoding RNA molecules which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, only recently there appeared an increased interest in the understanding of their regulatory importance. Among their most relevant characteristics are high stability, abundance and evolutionary conservation among species. CircRNAs are implicated in several cellular functions, ranging from miRNA and protein sponges to transcriptional modulation and splicing. Additionally, circRNAs' aberrant expression in pathological conditions is bringing to light their possible use as diagnostic and prognostic biomarkers. Their use as indicator molecules of pathological changes is also supported by their peculiar covalent closed cyclic structure which bestows resistance to RNases. Their regulatory role in cancer pathogenesis and metastasis is supported by studies involving human tumors that have investigated different expression profiles of these molecules. As endogenous competitive RNA, circRNAs can regulate tumor proliferation and invasion and they arouse great consideration as potential therapeutic biomarkers and targets for cancer. In this review, we describe the most recent findings on circRNAs in the most common pediatric solid cancers (such as brain tumors, neuroblastomas, and sarcomas) and in more rare ones (such as Wilms tumors, hepatoblastomas, and retinoblastomas).

PMID:36672544 | PMC:PMC9856195 | DOI:10.3390/biomedicines11010036

Intraluminal Small Bowel Metastasis From Primary Lung Cancer

Fetched: January 21st, 2023, 5:01am GMT by Nina D Kosciuszek

World J Oncol. 2022 Dec;13(6):409-416. doi: 10.14740/wjon1532. Epub 2022 Dec 24.

ABSTRACT

Lung cancer is the leading cause of cancer-related death worldwide, with frequent metastases to the brain, liver, adrenal glands, and bone. The incidence of intraluminal small bowel metastases of the lung is extremely rare and poorly documented within the literature. Few case studies have been published since the late 1980s and early 1990s. However, little is known about this rare form of metastasis. Small bowel metastatic disease has atypical symptoms that mimic a variety of other diseases; as a result, signs and symptoms may be overlooked until the disease has progressed to a late stage. Signs of small bowel obstruction, symptomatic anemia, abdominal pain, and peritonitis are commonly reported signs and symptoms. Various modalities can be utilized for the workup of suspected small bowel metastasis, including positron emission tomography, computed tomography, and various forms of endoscopy. The prognosis for lung cancer patients with intestinal metastases is poor, with many only surviving months to a few years after diagnosis. Therefore, it is critical to consider small bowel masses as a differential diagnosis in a patient with primary lung cancer who demonstrates clinical signs consistent with symptomatic anemia secondary to gastrointestinal (GI) bleeding, peritonitis, or small bowel obstruction. We report an unusual case of intraluminal and fungating small bowel masses in a patient who had previously undergone lung resections and chemo-immunotherapy. She was diagnosed with non-small undifferentiated carcinoma with tumor necrosis over 12 years before disease recurrence in the bilateral lungs, right adrenal gland, bone, and small bowel. The discovery of the small bowel metastases occurred while undergoing treatment for advanced-stage disease. At this time, she completed chemo-immunotherapy and remained on maintenance immunotherapy. The patient also underwent a partial right adrenalectomy and radiotherapy to the right adrenal gland. Given that she was experiencing symptomatic anemia and further workup indicated that the GI masses were causing her anemia, she underwent palliative small bowel resection of the masses. The pathology results demonstrated that the masses originated from her primary lung cancer, confirming metastatic disease to the small bowel.

PMID:36660214 | PMC:PMC9822679 | DOI:10.14740/wjon1532

Permalink for 'Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma'

Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma

Fetched: January 20th, 2023, 5:01am GMT by Zihao Wang

Neuro Oncol. 2023 Jan 19:noad017. doi: 10.1093/neuonc/noad017. Online ahead of print.

ABSTRACT

BACKGROUND: Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined.

METHODS: The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data, indicating high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines.

RESULTS: Differences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and its biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital (PUMCH). We further evaluated the clinical significance of BM-index and identified 7 drugs that potentially target BMAECs.

CONCLUSIONS: This study clarified possible cellular origins and drivers of metastatic LUAD at single cell level, and laid a foundation for early detections of LUAD patients with a high risk of BM.

PMID:36656750 | DOI:10.1093/neuonc/noad017

Permalink for 'Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy'

Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy

Fetched: January 20th, 2023, 5:01am GMT by Ann-Shung Lieu

Indian J Pathol Microbiol. 2023 Jan-Mar;66(1):141-144. doi: 10.4103/ijpm.ijpm_817_21.

ABSTRACT

Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis after subtotal tumor resection and adjuvant radiotherapy. This case was a 58-year-old male with an unsteady gait for 2 months. Enhanced brain magnetic resonance imaging revealed a heterogeneous mass involving the pineal region. The initial pathological diagnosis of pineocytoma was confirmed after subtotal tumor resection. Two years after adjuvant radiotherapy to the primary site, the magnetic resonance imaging showed C2 and T2 metastatic lesions, with the final pathological diagnosis being pineal parenchymal tumor (PPT) with intermediate differentiation after the removal of T2 intramedullary tumor. After that adjuvant radiotherapy at the cervical and thoracic spinal cord was completed. There was no recurrence of the tumor 1 year after the radiotherapy. We report a rare case of pineocytoma with malignant transformation to PPT with intermediate differentiation and leptomeningeal dissemination.

PMID:36656225 | DOI:10.4103/ijpm.ijpm_817_21

Adrenal Liposarcoma: A Novel Presentation of Multiple Endocrine Neoplasia Type 1

Fetched: January 20th, 2023, 5:01am GMT by Teodor Duro

AACE Clin Case Rep. 2022 Nov 13;9(1):10-12. doi: 10.1016/j.aace.2022.11.003. eCollection 2023 Jan-Feb.

ABSTRACT

BACKGROUND/OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) syndrome results from genetic sequence variations of the tumor suppressor MEN1 gene, which codes for the protein menin. Individuals with MEN1 are prone to developing multiple tumors involving the endocrine and nonendocrine organs. MEN1 associated with liposarcomas has not been documented previously. We highlight a case of MEN1 presenting with a metastatic adrenal liposarcoma.

CASE REPORT: A 41-year-old Hispanic man with a history of nephrolithiasis and skin lesions presented to the emergency department with abdominal pain. He was found to have a right adrenal mass measuring 7.9 cm with extension into the liver and primary hyperparathyroidism. He had multiple paternal first-degree relatives with similar skin lesions, hypercalcemia, and tumors of the brain, thoracic cavity, abdomen, and thyroid. The mass was identified as a metastatic pleiomorphic adrenal liposarcoma on surgical pathology. Genetic testing revealed a germline pathogenic sequence variation of the MEN1 gene.

DISCUSSION: Liposarcomas are rare malignant tumors with an annual incidence of 2.5 cases per 1 million. Although lipoma formation is a commonly described manifestation of MEN1, liposarcomas have not been associated with MEN1 previously. A potential mechanism of this association is through the role of menin in inducing adipocyte differentiation via peroxisome proliferator-activated receptor-γ activation, a highly expressed protein in liposarcomas.

CONCLUSION: Liposarcomas should be included in the differential of MEN1-related tumors.

PMID:36654999 | PMC:PMC9837086 | DOI:10.1016/j.aace.2022.11.003

Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series

Fetched: January 19th, 2023, 5:01am GMT by Yuji Kibe

Sci Rep. 2023 Jan 16;13(1):23. doi: 10.1038/s41598-022-25928-2.

ABSTRACT

Isocitrate dehydrogenase wild-type (IDHwt) diffuse astrocytomas feature highly infiltrative patterns, such as a gliomatosis cerebri growth pattern with widespread involvement. Among these tumors, localized IDHwt histologically diffuse astrocytomas are rarer than the infiltrative type. The aim of this study was to assess and describe the clinical, radiographic, histopathological, and molecular characteristics of this rare type of IDHwt histologically diffuse astrocytomas and thereby provide more information on how its features affect clinical prognoses and outcomes. We retrospectively analyzed the records of five patients with localized IDHwt histologically diffuse astrocytomas between July 2017 and January 2020. All patients were female, and their mean age at the time of the initial treatment was 55.0 years. All patients had focal disease that did not include gliomatosis cerebri or multifocal disease. All patients received a histopathological diagnosis of diffuse astrocytomas at the time of the initial treatment. For recurrent tumors, second surgeries were performed at a mean of 12.4 months after the initial surgery. A histopathological diagnosis of glioblastoma was made in four patients and one of gliosarcoma in one patient. The initial status of IDH1, IDH2, H3F3A, HIST1H3B, and BRAF was "wild-type" in all patients. TERT promoter mutations (C250T or C228T) were detected in four patients. No tumors harbored a 1p/19q codeletion, EGFR amplification, or chromosome 7 gain/10 loss (+ 7/ - 10). We assessed clinical cases of localized IDHwt histologically diffuse astrocytomas that resulted in malignant recurrence and a poor clinical prognosis similar to that of glioblastomas. Our case series suggests that even in patients with histologically diffuse astrocytomas and those who present with radiographic imaging findings suggestive of a localized tumor mass, physicians should consider the possibility of IDHwt histologically diffuse astrocytomas.

PMID:36646712 | PMC:PMC9842655 | DOI:10.1038/s41598-022-25928-2

How to treat histone 3 altered gliomas: molecular landscape and therapeutic developments

Fetched: January 19th, 2023, 5:01am GMT by Vincenzo Di Nunno

Expert Rev Clin Pharmacol. 2023 Jan;16(1):17-26. doi: 10.1080/17512433.2023.2163385. Epub 2022 Dec 28.

ABSTRACT

INTRODUCTION: Diffuse midline gliomas (DMG) and diffuse hemispheric glioma (DHG) are both rare tumors characterized and recognized for specific alterations of histone 3 including H3K27 (DMG) and H3G34 (DHG). Despite these tumors arising from alterations of the same gene their clinical, radiological, and molecular behaviors strongly diverge, requiring a personalized therapeutic approach.

AREAS COVERED: We performed a review on Medline/PudMed aiming to search papers relative to prospective trials, retrospective studies, case series, and case reports of interest in order to investigate current knowledge toward the main clinical and molecular characteristics, radiology, and diagnosis, loco-regional and systemic treatments of these tumors. Moreover, we also evaluated the novel treatments under investigation.

EXPERT OPINION: Thanks to an increased knowledge of the genomic landscape of these rare tumors, there are novels promising therapeutic targets for these malignancies. However, the majority of available trials allowed enrollment only in DMG, while few studies are focused on or allow the inclusion of DHG patients.

PMID:36576307 | DOI:10.1080/17512433.2023.2163385

Permalink for 'Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease'

Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease

Fetched: January 18th, 2023, 5:01am GMT by Emily Marshall

Neoplasia. 2023 Jan 15;37:100873. doi: 10.1016/j.neo.2022.100873. Online ahead of print.

ABSTRACT

INTRODUCTION: Craniopharyngioma is a rare, low-grade tumor located in the suprasellar region of the brain, near critical structures like the pituitary gland. Here, we concurrently investigate the status of clinical and genomic data in a retrospective craniopharyngioma cohort and survey-based data to better understand patient-relevant outcomes associated with existing therapies and provide a foundation to inform new treatment strategies.

METHODS: Clinical, genomic, and outcome data for a retrospective cohort of patients with craniopharyngioma were collected and reviewed through the Children's Brain Tumor Network (CBTN) database. An anonymous survey was distributed to patients and families with a diagnosis of craniopharyngioma to understand their experiences throughout diagnosis and treatment.

RESULTS: The CBTN repository revealed a large proportion of patients (40 - 70%) with specimens that are available for sequencing but lacked relevant quality of life (QoL) and functional outcomes. Frequencies of reported patient comorbidities ranged from 20 to 25%, which is significantly lower than historically reported. Survey results from 159 patients/families identified differences in treatment considerations at time of diagnosis versus time of recurrence. In retrospective review, patients and families identified preference for therapy that would improve QoL, rather than decrease risk of recurrence (mean 3.9 vs. 4.4 of 5) and identified endocrine issues as having the greatest impact on patients' lives.

CONCLUSIONS: This work highlights the importance of prospective collection of QoL and functional metrics alongside robust clinical and molecular correlates in individuals with craniopharyngioma. Such comprehensive measures will facilitate biologically relevant therapeutic strategies that also prioritize patient needs.

PMID:36649671 | PMC:PMC9852952 | DOI:10.1016/j.neo.2022.100873

Permalink for 'Primary central nervous system lymphoma of the third ventricle with intra-tumoral hemorrhage: A case report and literature review'

Primary central nervous system lymphoma of the third ventricle with intra-tumoral hemorrhage: A case report and literature review

Fetched: January 17th, 2023, 5:01am GMT by Yu Muroya

Oncol Lett. 2022 Dec 15;25(2):47. doi: 10.3892/ol.2022.13633. eCollection 2023 Feb.

ABSTRACT

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor that most commonly arises in the cerebral white matter, basal ganglia, peri-ventricle or corpus callosum. Confinement of PCNSL to the third ventricle is extremely rare, and seldom presents with intratumoral hemorrhage (ITH). The present study described the case of a 75-year-old woman who presented with obstructive hydrocephalus due to third-ventricle PCNSL. On magnetic resonance imaging (MRI), the tumor presented ITH on T2*-weighted images and a highly elevated regional cerebral blood volume on dynamic susceptibility contrast-enhanced MRI (DSC-MRI). Due to the high elevation of the regional cerebral blood volume, high-grade glioma was suspected as a preoperative diagnosis. The patient underwent endoscopic tumor biopsy and third ventricle PCNSL was successfully diagnosed. The patient achieved good prognosis at an early stage after the start of treatment initiation. There are many differential considerations for a third-ventricle tumor, and DSC-MRI can help the differential diagnosis of these tumors. Furthermore, the presence of ITH can lead to the inaccurate estimation of regional cerebral blood volume values. Overall, silent or microhemorrhage in PCNSL may be underestimated, and clinicians should therefore carefully evaluate tumor vascularity by MRI.

PMID:36644156 | PMC:PMC9811644 | DOI:10.3892/ol.2022.13633

Midline brain hamartomatous lesions in fibrodysplasia ossificans progressiva with ACVR1 mutations

Fetched: January 17th, 2023, 5:01am GMT by Jesse Lee Kresak

Neuropathology. 2023 Jan 15. doi: 10.1111/neup.12892. Online ahead of print.

ABSTRACT

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by extensive heterotopic ossification of soft tissue structures leading to severe limitations in movement. FOP is caused by a germline mutation in the activating receptor type IA (ACVR1) gene. Worrisome is the fact that up to a third of diffuse intrinsic pontine gliomas (DIPG) also harbor the same point mutation in ACVR1. Radiological reports of central nervous system (CNS) involvement by FOP have described brainstem masses; however, the literature on the histopathology or pathogenesis of these lesions is scant. Here we present detailed neuropathologic findings of a brainstem mass in a patient with FOP and suggest that the tumor is hamartomatous in nature. This report, along with a literature review of radiographic and laboratory data, offers support for the idea that the ACVR1 mutation may incite CNS proliferation, predominantly in the brainstem, but is probably not an oncologic driver. These lesions may be seen at autopsy and are likely noncontributory to death.

PMID:36642816 | DOI:10.1111/neup.12892

Carcinomatous meningitis from ovarian serous carcinoma: A case report

Fetched: January 17th, 2023, 5:01am GMT by Eijiro Uchikura

Oncol Lett. 2022 Dec 23;25(2):66. doi: 10.3892/ol.2022.13652. eCollection 2023 Feb.

ABSTRACT

Multifocal dissemination of cancer cells from the primary tumor sites to the subarachnoid, pia mater and cerebrospinal fluid (CSF) of the brain and spinal cord causes carcinomatous meningitis (CM). CM is rarely observed in patients with gynecological cancer. The present study described a 59-year-old woman who was diagnosed with CM as a recurrence of stage IIIC ovarian cancer, after presenting with headache and decreased level of consciousness. During adjuvant therapy following surgical debulking, she developed nausea and vomiting. The post-contrast fluid-attenuated inversion-recovery magnetic resonance imaging showed leptomeningeal enhancement on all sulci, particularly around the falx cerebri and cerebellar hemisphere. CM was suspected and CSF cytology revealed adenocarcinoma cells, thus confirming the diagnosis. Overall, although CM is rare, clinicians should be aware of this complication when patients with malignancies experience neurological symptoms, including headache, nausea and vomiting. Knowledge of this clinical entity should assist clinicians in ascertaining accurate diagnoses.

PMID:36644158 | PMC:PMC9827457 | DOI:10.3892/ol.2022.13652

Surgical Management of Peripheral Nerve Pathology in Patients With Neurofibromatosis Type 2

Fetched: January 13th, 2023, 4:18pm GMT by Matthieu Peyre

Neurosurgery. 2023 Feb 1;92(2):317-328. doi: 10.1227/neu.0000000000002202. Epub 2022 Nov 10.

ABSTRACT

BACKGROUND: Neurofibromatosis type 2 (NF2) is rare genetic disorder mainly characterized by the development of central nervous system lesions, but peripheral nerve pathology may also cause high morbidity including pain, motor, and sensory loss.

OBJECTIVE: To describe the tumor burden of patients with peripheral nerve pathology in NF2 including peripheral neuropathies and schwannomas and the results of surgery in the latter group.

METHODS: We conducted a retrospective chart review of all patients with NF2 followed up at our NF2 Reference Center to include all patients suffering from peripheral nerve pathology. Tumor detection relied on focal MRIs based on symptoms.

RESULTS: Thirty-four patients harboring 105 peripheral nerve schwannomas and 1 perineurioma were included. Schwannomas were mainly located in major nerves (n = 74, 71%) compared with subcutaneous (n = 23, 22%) and intramuscular (n = 8, 7%) cases. Most schwannomas (81/90-90%) were classical discrete tumors while multinodular cases represented only 9 cases (10%). During follow-up, 63 (60%) tumors were operated in 24 patients, including 39 schwannomas of major nerves. A complete resection was achieved in most of the cases (52/63, 83%) with a complete relief of preoperative pain in most patients (57/60, 95%). Persistent motor deficits (5/39, 13%) were mostly encountered in patients operated from multinodular schwannomas (4/5, 80%). Six patients had an associated peripheral neuropathy with 5 cases of pseudo-Charcot-Marie-Tooth-associated amyotrophy.

CONCLUSION: Surgery remains a safe and effective method of treating peripheral nerve schwannoma-associated pain in NF2, with the exception of rare multinodular tumors. Special attention should be drawn to patients harboring severely debilitating neuropathies and perineuriomas.

PMID:36637268 | DOI:10.1227/neu.0000000000002202

Two Cases of Rare Intratumoral Hemorrhage Following COVID-19 Vaccination

Fetched: January 13th, 2023, 2:06pm GMT by Shin Sugasawa

Cureus. 2022 Dec 11;14(12):e32400. doi: 10.7759/cureus.32400. eCollection 2022 Dec.

ABSTRACT

The increase in the rate of mRNA vaccination against coronavirus disease 2019 (COVID-19) worldwide has been accompanied by reports of an increase in the side effects of the vaccine. In the field of neurosurgery, several cases of venous thrombosis have been reported as possible complications after COVID-19 vaccination. However, no such side effects have been reported in patients with brain tumors, and COVID-19 vaccination is considered safe for this patient population. In this report, we present the cases of two patients with brain tumors who experienced intratumoral hemorrhage as a possible side effect of the COVID-19 vaccine. In the first case, a 54-year-old man who had received CyberKnife treatment for a vestibular schwannoma eight years prior presented with tongue discomfort, right-side facial numbness, and dizziness since the day after his COVID-19 vaccination. MRI revealed intratumoral hemorrhage of the vestibular schwannoma. The second patient was a 60-year-old woman who presented with a sudden-onset headache and vomiting that had started three days after her COVID-19 vaccination. CT revealed a meningioma with intratumoral hemorrhage. Both patients had undergone surgery prior to this presentation, and their symptoms had improved. They had no risk factors for intratumoral hemorrhage, suggesting that it may be a side effect of the mRNA vaccine against COVID-19. Although the causal relationship is unclear, acute inflammation with predominantly lymphocytic infiltration and thrombogenicity after COVID-19 vaccination may damage the fragile microcirculation of the tumor.

PMID:36636529 | PMC:PMC9831113 | DOI:10.7759/cureus.32400

Permalink for 'Posterior fossa giant adenoid cystic carcinoma with skull base invasion mimicking glomus jugulare: A case report and review of literature'

Posterior fossa giant adenoid cystic carcinoma with skull base invasion mimicking glomus jugulare: A case report and review of literature

Fetched: January 13th, 2023, 2:06pm GMT by Anand Kumar Das

Rare Tumors. 2023 Jan 6;15:20363613221150218. doi: 10.1177/20363613221150218. eCollection 2023.

ABSTRACT

The author describes a rare case of giant adenoid cystic carcinoma (ACC) mimicking large paraganglioma with lower cranial nerve palsy. A 60-year-old female presented with a progressive increase in postauricular swelling with unilateral hearing loss, facial deviation, difficulty in swallowing, and hoarseness of voice. MRI brain showed highly vascular infiltrating and osteolytic mass suggestive of large glomus jugulare versus sarcoma. It was completely engulfing the jugular foramen and lower cranial nerves with bony erosion of the jugular foramen and occipital condyle. The whole mastoid was filled with the tumor. On digital subtraction angiography the majority of blood supply was from the occipital branch of the external carotid artery and vertebral artery. The patient underwent percutaneous embolization followed by external carotid ligation and resection of the mass. The postoperative course was uneventful. Histopathology was suggestive of mixed ACCs. The patient received radiotherapy. After 1 year of follow up no recurrence or distant metastasis was noted.

PMID:36636105 | PMC:PMC9830093 | DOI:10.1177/20363613221150218

A case of pituitary gland abscess associated with granulomatous hypophysitis

Fetched: January 13th, 2023, 2:06pm GMT by Mohammad Mahdi Rabiei

BMC Neurol. 2023 Jan 12;23(1):11. doi: 10.1186/s12883-023-03060-6.

ABSTRACT

BACKGROUND: Granulomatous hypophysitis is a rare disease that presents with chronic inflammation of the pituitary gland. In this study, we reported a case of granulomatous hypophysitis associated with a pituitary abscess.

CASE PRESENTATION: A 39-year-old woman presented with a 2-year history of infertility. For the past six months, she has suffered from amenorrhea, decreased libido, headaches, and vertigo. She was referred to our hospital with a suspected diagnosis of nonfunctioning pituitary adenoma based on her presentation and brain MRI findings. She underwent trans-sphenoidal surgery (TSS). Direct observation during surgery revealed drainage of malodor pus and pituitary gland abscess. The histopathological evaluation also showed granulomatous hypophysitis and neutrophilic microabscess formation. The patient was initially treated with high doses of ceftriaxone (2 g twice daily) and metronidazole (500 mg (mg) four times per day). Also, the patient received cortisol replacement therapy after the operation. After obtaining the antibiogram and culture results, the treatment regimen was continued for 4 weeks postoperatively, followed by amoxicillin-clavulanate (500/125 mg three times daily) for a total duration of 12 weeks.

CONCLUSION: The patient recovered uneventfully and the postoperative MRI was normal without any remnant lesions.

PMID:36631799 | PMC:PMC9835326 | DOI:10.1186/s12883-023-03060-6

Permalink for 'A multiphoton transition activated iron based metal organic framework for synergistic therapy of photodynamic therapy/chemodynamic therapy/chemotherapy for orthotopic gliomas'

A multiphoton transition activated iron based metal organic framework for synergistic therapy of photodynamic therapy/chemodynamic therapy/chemotherapy for orthotopic gliomas

Fetched: January 12th, 2023, 5:01am GMT by Zhijia Lv

J Mater Chem B. 2023 Jan 11. doi: 10.1039/d2tb02273g. Online ahead of print.

ABSTRACT

Although photodynamic therapy (PDT) has exhibited good potential in therapy of gliomas, the limited penetration depth of light and the obstacle of the blood-brain barrier (BBB) lead to unsatisfactory treatment effects. Herein, a multifunctional nanodrug (UMD) was constructed with up-conversion nanoparticles (NaGdF4:Yb,Tm@NaYF4:Yb,Nd@NaYF4, UCNPs) as the core, the photosensitizer NH2-MIL-53 (Fe) as the shell and a carrier for loading chemotherapy drug doxorubicin hydrochloride (Dox) for synergistic therapy of gliomas. Lactoferrin (LF) was finally modified on the surface of the UMD to endow it with the ability to traverse the BBB and target cells (UMDL). The UCNP core can convert 808 nm near-infrared (NIR) light to ultraviolet light (UV light) for exciting NH2-MIL-53 (Fe), achieving NIR-mediated PDT. In addition, Fe³⁺ on the surface of the NH2-MIL-53 (Fe) shell could be reduced to Fe²⁺ in a tumor microenvironment (TME), and then reacted with over-expressed H2O2 in the TME to generate hydroxyl radicals (˙OH) for chemodynamic therapy (CDT). The Dox drug could be released in response to acidic conditions in the TME, inhibiting the growth of gliomas with low side effects. The synergistic effect of PDT/CDT/chemotherapy leads to effective suppression of orthotopic gliomas.

PMID:36629834 | DOI:10.1039/d2tb02273g

Oligodendroglioma metastasizing to cervical lymph node: Rare entity diagnosed on fine-needle aspiration cytology

Fetched: January 12th, 2023, 5:01am GMT by Sant Prakash Kataria

Diagn Cytopathol. 2023 Jan 11. doi: 10.1002/dc.25100. Online ahead of print.

ABSTRACT

Extra neural metastasis of central nervous system oligodendroglioma is very rare. Oligodendroglioma is the seventh most frequently occurring neoplasm of central nervous system (CNS) with metastasis outside the CNS. According to literature, presence of metastasis in CNS was most frequently detected in patients of glioblastoma (41.4%), medulloblastoma (26.7%), ependymomas (16.4%), astrocytoma (10.3%) and oligodendroglioma (5.27%). A 38-year-old male patient presented with loss of vision and swelling on left side of neck since last 1 week measuring 3 x 2 cm. He was operated for brain tumor 7 years back, which was diagnosed as oligodendroglioma. Ultrasound sonography revealed multiple hypoechoic lymph nodes in bilateral cervical region largest measuring 4.5 x 1.9 cm in left submandibular region. FNA of left submandibular lymph node was done, which revealed deposits of poorly differentiated malignancy. Cell block was prepared for carrying out ancillary studies which showed positivity for glial fibrillary acidic protein (GFAP), S-100 and negativity for cytokeratin (CK), epithelial membrane antigen (EMA), LCA and progesterone receptor (PR). Based on previous history of oligodendroglioma, cytological and immunohistochemistry (IHC) findings a diagnosis of metastatic oligodendroglioma was made. Metastasis of oligodendroglioma to cervical lymph node should also be considered as one of the differential diagnoses. Diagnosing metastatic CNS tumor is extremely challenging for pathologists. It is essential to have the clinical information of a previous CNS tumor, including the histologic type and immunophenotype. Besides common malignancies of cervical lymph node, we should also think of CNS metastasis so that patient management will be early and proper.

PMID:36628997 | DOI:10.1002/dc.25100

Virtual Trials: Causally-validated treatment effects efficiently learned from an observational cancer registry

Fetched: January 12th, 2023, 5:01am GMT by Asher Wasserman

Artif Intell Med. 2023 Jan;135:102450. doi: 10.1016/j.artmed.2022.102450. Epub 2022 Nov 22.

ABSTRACT

Randomized controlled trials (RCTs) offer a clear causal interpretation of treatment effects, but are inefficient in terms of information gain per patient. Moreover, because they are intended to test cohort-level effects, RCTs rarely provide information to support precision medicine, which strives to choose the best treatment for an individual patient. If causal information could be efficiently extracted from widely available real-world data, the rapidity of treatment validation could be increased, and its costs reduced. Moreover, inferences could be made across larger, more diverse patient populations. We created a "virtual trial" by fitting a multilevel Bayesian survival model to treatment and outcome records self-reported by 451 brain cancer patients. The model recovers group-level treatment effects comparable to RCTs representing over 3200 patients. The model additionally discovers the feature-treatment interactions needed to make individual-level predictions for precision medicine. By learning from heterogeneous real-world data, virtual trials can generate more causal estimates with fewer patients than RCTs, and they can do so without artificially limiting the patient population. This demonstrates the value of virtual trials as a complement to large randomized controlled trials, especially in highly heterogeneous or rare diseases.

PMID:36628781 | DOI:10.1016/j.artmed.2022.102450

Ectopic recurrence of craniopharyngioma in the posterior fossa: Case report and review of the literature

Fetched: January 12th, 2023, 5:01am GMT by Antonio Selfa

Neurocirugia (Astur : Engl Ed). 2023 Jan-Feb;34(1):32-39. doi: 10.1016/j.neucie.2022.11.001.

ABSTRACT

Craniopharyngiomas are benign epithelial tumors which may very occasionally recur in ectopic locations. We present two cases of ectopic recurrence, both in the posterior fossa, and provide a review of the literature with basic statistics. Two patients admitted to our institution with posterior fossa lesions underwent gross total resection. Pathological studies showed adamantinomatous craniopharyngiomas (ACP). Both patients had a prior history of suprasellar tumor surgery. We also reviewed the related data and undertook a basic statistical analysis. We found 67 cases of ectopic recurrent craniopharyngioma (including the present cases): 51 cases were adamantinomatous (76%), 6 papillary (9%) and 10 unknown (15%). 18 cases occurred in the posterior fossa, all of them diagnosed as the ACP subtype. The intervals until recurrence were 15.15 years for posterior fossa recurrences and 5.75 years for supratentorial cases. Student t test showed significant differences in time to recurrence (p 0.002). Gross total resection was performed in 53 cases (79%), subtotal resection+radiotherapy in 3 (5%) and 11 (16%) cases were treated with other options. Ectopic recurrence is a rare but possible event. Those in the posterior fossa may appear later than in the supratentorial space. ACP is likely to be the most common subtype in these cases, possibly due to its more aggressive behavior compared to the papillary subtype. Long term follow-up should be performed to detect ectopic recurrences. Ectopic recurrences are often surgically accessible and gross total resection should be achieved.

PMID:36623891 | DOI:10.1016/j.neucie.2022.11.001

Permalink for 'Clinical and genetic diagnosis of Cowden syndrome: A case report of a rare PTEN germline variant and diverse clinical presentation'

Clinical and genetic diagnosis of Cowden syndrome: A case report of a rare PTEN germline variant and diverse clinical presentation

Fetched: January 11th, 2023, 5:01am GMT by Hironori Arai

Medicine (Baltimore). 2023 Jan 6;102(1):e32572. doi: 10.1097/MD.0000000000032572.

ABSTRACT

INTRODUCTION: Cowden syndrome is a rare autosomal dominant disease characterized by the development of hamartomas and increased risks of other tumors, including breast, thyroid, and uterine cancers. Most patients with Cowden syndrome show mutations of the phosphatase and tensin homolog (PTEN) gene on chromosome 10; however, some patients with mutations do not show clinical symptoms, while patients with clinical symptoms may not have detectable PTEN mutations.

CASE PRESENTATION: A 39-year-old woman with macrocephaly had previously been diagnosed with Cowden syndrome at another hospital, when she presented with the onset of breast cancer. A wide variety of complications were detected, including cerebellar tumors treated by resection, hydrocephalus, and multiple polyps in the stomach and large intestine. She was further diagnosed with adult-onset Lhermitte-Duclos disease as a complication of Cowden syndrome. She subsequently developed a dural arteriovenous fistula treated by transvenous embolization. After transfer to our hospital, she developed adenomatous goiter treated by resection, recurrent breast cancer treated with hormonal therapy, and multifocal oral mucosal papillomatosis. Her older sister had previously been diagnosed with Cowden syndrome and her father was undiagnosed but had macrocephaly, hydrocephalus, and multifocal oral mucosal papillomatosis, suggestive of Cowden syndrome. After consultation with a genetic specialist, analysis of the PTEN gene showed a rare but likely pathogenic germline c.801 + 2T>A variant located at the splice donor site of intron 7. The patient's clinical diagnosis of Cowden syndrome was accordingly confirmed by the genetic findings. Appropriate surveillance procedures were put in place to detect any further tumors.

CONCLUSIONS: The clinical symptoms of Cowden syndrome do not always correlate with the genetic results. However, recent improvements in genetic testing suggest the importance of diagnosing this disease using both clinical and genetic approaches, in collaboration with genetic experts, to ensure an accurate diagnosis and appropriate surveillance for malignant tumors.

PMID:36607858 | PMC:PMC9829268 | DOI:10.1097/MD.0000000000032572

Permalink for 'Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review'

Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review

Fetched: January 11th, 2023, 5:01am GMT by Ji-Xin Fu

Medicine (Baltimore). 2022 Dec 9;101(49):e31866. doi: 10.1097/MD.0000000000031866.

ABSTRACT

RATIONALE: Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in the world. The most common metastatic sites of LC are the brain (47%), bone (36%), liver (22%), adrenal glands (15%), thoracic cavity (11%) and distant lymph nodes (10%). Peritoneal carcinomatosis (PC) is a rare clinical event in LC patients. Considering the rarity and nonspecific clinical symptoms of peritoneal metastasis among LC patients, a case of peritoneal metastasis secondary to LC incidentally observed by laparoscopic appendectomy is unusual.

PATIENT CONCERNS: Here, we present a 53-year-old never-smoker woman who presented to the emergency department with a 2-day history of pain in the right abdominal quadrant. Later, laparoscopy revealed acute suppurative appendicitis accompanied by a peritoneal metastatic mass.

DIAGNOSIS: The patient was diagnosed with PC secondary to metastatic LC complicated with acute suppurative appendicitis by immunohistochemistry. Positron emission tomography computed tomography (PET CT) findings further strengthen the evidence of PC from LC.

OUTCOMES: Based on the results of genomic analysis, the patient received targeted therapy with osimertinib 80 mg/d.

LESSONS: Due to the discovery of new targets, the use of molecular therapies improved progression-free survival (PFS) and overall survival (OS), which increases the chance of identifying peritoneal metastasis of LC. For LC patients with abdominal symptoms, clinicians should be aware of the possibility of peritoneal metastasis from LC, especially for patients diagnosed with lung adenocarcinoma or with pleural effusion.

PMID:36626502 | PMC:PMC9750620 | DOI:10.1097/MD.0000000000031866

Current Approaches to Craniopharyngioma Management

Fetched: January 11th, 2023, 5:01am GMT by Michael Joseph Diaz

Front Biosci (Landmark Ed). 2022 Dec 21;27(12):328. doi: 10.31083/j.fbl2712328.

ABSTRACT

Craniopharyngiomas (CP) are rare noncancerous brain tumors located in the skull base. To date, CP remain challenging-to-resect tumors, owing to their difficult location and invasive potential, with profound adverse effects for the patient if left to grow. Indeed, gross total resection may also be accompanied by unwelcome sequalae, underscoring the need for continued investigation. In the present work, we provide a scoping review of current CP management, with emphasis on our knowledge of their genesis, available treatment options, post-intervention clinical outcomes. Leading theories of CP development are (1) the embryonic theory, explaining the development of adamantinomatous CP from epithelial remnants of Rathke's pouch and (2) the metaplastic theory, which describes papillary CP development as a result of adenohypophyseal cell metaplasia. Treatment may include surgery, intracystic therapy, or irradiation depending on tumor size, history and location. However, whether a single ideal approach and timing for CP intervention exists remains debated. We appraise and critique these areas with priority for emerging basic results and innovation.

PMID:36624954 | PMC:PMC9835013 | DOI:10.31083/j.fbl2712328

Nomogram for predicting survival of patients with anaplastic ependymoma in the brain and spinal cord

Fetched: January 10th, 2023, 5:01am GMT by Liu Hui

Turk Neurosurg. 2022 Jul 27. doi: 10.5137/1019-5149.JTN.41103-22.1. Online ahead of print.

ABSTRACT

AIM: Anaplastic ependymoma is a rare tumor. Although this tumor is rare, it still has high research value. Based on current knowledge, articles on anaplastic ependymoma in the brain and spinal cord are extremely limited.

MATERIAL AND METHODS: We retrospectively extracted data of 305 patients with anaplastic ependymoma in the brain and spinal cord from the Surveillance, Epidemiology, and End Results database (SEER) between 1988 and 2015, which was analyzed in R software. The statistical significance indicators were identified by the COX regression analysis. The Nomogram visualized the model and was corrected by the C-index, AUC and calibration curve.

RESULTS: The results of the analysis showed age and treatment were found to be statistical significance in this study. Based on this study, the model\'s C-index was 0.777, and the area under the curve (AUC) value of the time-dependent ROC curve at 2-Year, 3-Year, and 5-Year was 0.758, 0.775 and 0.788. These showed a good discriminatory ability. Finally, a nomogram was constructed. And the nomogram was validated by validation curve.

CONCLUSION: At last, the two risk factors (including age and treatment) were identified to the independent prognostic factors for patients with anaplastic ependyma in the spinal cord and brain. Meanwhile, our model can accurately assess the disease-specific survival rate of these patients, and can provide recommendations on treatment options.

PMID:36622192 | DOI:10.5137/1019-5149.JTN.41103-22.1

Let Us Not Forget About Bleeding: A Case Report and Brief Literature Review on Hemorrhagic Vestibular Schwannoma

Fetched: January 10th, 2023, 5:01am GMT by Francisco Alves de Sousa

Cureus. 2022 Dec 6;14(12):e32269. doi: 10.7759/cureus.32269. eCollection 2022 Dec.

ABSTRACT

Hemorrhagic vestibular schwannoma (HVS) consisting of acute intratumoral and subarachnoid hemorrhage is a rare phenomenon. We present the case of a 31-year-old woman who attended the Otorhinolaryngology department with right-sided intense tinnitus, dizziness, imbalance, and headache. Brain computed tomography revealed a spontaneous hyperdensity in the posterior fossa with marked deformation of the brainstem, middle cerebral peduncle, and cerebellum, with the near collapse of the fourth ventricle. Ophthalmology evaluation confirmed bilateral papilledema. Brain magnetic resonance imaging confirmed a voluminous 33 x 28 x 29 mm extra-axial lesion centered on the right pontine-cerebellar angle cistern, extending from the plane of the trigeminal nerve/tent of the cerebellum. The acoustic pore was enlarged. The patient underwent retrosigmoid craniotomy and microscopic tumor resection showing significant improvement in the follow-up. Pathological findings confirmed HVS. Delayed treatment of HVS can increase morbidity or even be fatal. The objective of this work is to describe and revise HVS, in order to bring awareness to this uncommon entity.

PMID:36620834 | PMC:PMC9815954 | DOI:10.7759/cureus.32269

Endoscopic endonasal resection of an epidermoid cyst in the cavernous sinus: A case report and literature review

Fetched: January 10th, 2023, 5:01am GMT by Yinzi Wu

Front Oncol. 2022 Dec 23;12:972573. doi: 10.3389/fonc.2022.972573. eCollection 2022.

ABSTRACT

BACKGROUND: Epidermoid cysts of cavernous sinus (CS) are rare congenital neoplasms of the central nervous system. In previous literature reports, the treatment for CS epidermoid cysts was mainly microsurgical resection, and the surgical methods included simple microsurgery and endoscope-assisted microsurgery. The present case report demonstrates the first case of complete resection of a CS epidermoid cyst by a simple endoscopic endonasal transcavernous (EET) approach.

CASE PRESENTATION: A 54-year-old woman presented with chronic persistent headaches and occasional syncope. Brain MRI demonstrated a space-occupying lesion of the left CS, and digital substruction angiography (DSA) showed a small aneurysm at the beginning of the left ophthalmic artery. Thrombotic therapy of carotid-ophthalmic aneurysms was performed first, and the patient underwent resection of the CS lesion secondary. Considering the location of the lesion and the neuroendoscopy technology and experience of the doctor, we made bold innovations and used an EET approach to achieve complete resection of the lesion. The postoperative pathological results were consistent with the characteristics of epidermoid cyst. During the 1-year follow up, the patient showed no apparent signs of recurrence on head MRI.

CONCLUSION: Epidermoid cyst of cavernous sinus is a rare benign occupying lesion in cavernous sinus. Reviewing the previous literature, the main treatment is microneurosurgery, and neuroendoscopy is only used as an auxiliary equipment. We present the first case of complete endoscopic resection of CS epidermoid cyst by EET approach according to CARE guidelines, aiming to share the new surgical plan for CS epidermoid cyst and provide more surgical options for this disease for neurosurgery colleagues.

PMID:36620550 | PMC:PMC9817098 | DOI:10.3389/fonc.2022.972573

Role of non-coding RNAs and exosomal non-coding RNAs in retinoblastoma progression

Fetched: January 10th, 2023, 5:01am GMT by Nasrin Ahangar Davoodi

Front Cell Dev Biol. 2022 Dec 23;10:1065837. doi: 10.3389/fcell.2022.1065837. eCollection 2022.

ABSTRACT

Retinoblastoma (RB) is a rare aggressive intraocular malignancy of childhood that has the potential to affect vision, and can even be fatal in some children. While the tumor can be controlled efficiently at early stages, metastatic tumors lead to high mortality. Non-coding RNAs (ncRNAs) are implicated in a number of physiological cellular process, including differentiation, proliferation, migration, and invasion, The deregulation of ncRNAs is correlated with several diseases, particularly cancer. ncRNAs are categorized into two main groups based on their length, i.e. short and long ncRNAs. Moreover, ncRNA deregulation has been demonstrated to play a role in the pathogenesis and development of RB. Several ncRNAs, such as miR-491-3p, miR-613,and SUSD2 have been found to act as tumor suppressor genes in RB, but other ncRNAs, such as circ-E2F3, NEAT1, and TUG1 act as tumor promoter genes. Understanding the regulatory mechanisms of ncRNAs can provide new opportunities for RB therapy. In the present review, we discuss the functional roles of the most important ncRNAs in RB, their interaction with the genes responsible for RB initiation and progression, and possible future clinical applications as diagnostic and prognostic tools or as therapeutic targets.

PMID:36619866 | PMC:PMC9816416 | DOI:10.3389/fcell.2022.1065837

Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease

Fetched: January 10th, 2023, 5:01am GMT by Christopher Cronin

Front Med (Lausanne). 2022 Dec 22;9:1070828. doi: 10.3389/fmed.2022.1070828. eCollection 2022.

ABSTRACT

BRAF V600E oncogene mutations have been reported in multiple central nervous system (CNS) tumor types, and emerging evidence supports the use of targeted therapy in BRAF-mutated gliomas. BRAF oncogene mutations have been recently identified in Rosai-Dorfman disease (RDD)-a rare non-Langerhans cell histiocytosis. This series describes three patients from two neurosurgical centers in Ireland with BRAF V600E-mutated CNS tumors. The study participants include a 19-year-old male patient with ganglioglioma with anaplastic features, a 21-year-old male patient with CNS involvement of RDD, and a 28-year-old female patient with ganglioglioma with anaplastic features. Two patients received radiation with concurrent temozolomide before BRAF-targeted therapy. This case series describes clinical and radiological responses to BRAF-targeted therapy in BRAF V600E-mutated gliomas across multiple tumor grades and is only the second published report of response to targeted therapy in BRAF-mutated RDD. The durability of disease control with BRAF-targeted therapy was generally superior to that achieved with chemoradiation; one patient has experienced ongoing disease control for 5 years. The reported case of treatment response in BRAF-mutated RDD supports the strategy of genotyping and utilization of targeted therapy in this rare disease. The optimal sequencing of BRAF-targeted therapy in BRAF-mutated gliomas/glioneuronal tumors remains unclear, and further prospective studies are required to guide the use of genome-matched therapy in this patient population.

PMID:36619621 | PMC:PMC9813211 | DOI:10.3389/fmed.2022.1070828

A rare pituitary tumor associated with hyperthyroidism and acromegaly

Fetched: January 10th, 2023, 5:01am GMT by Li Li

Front Endocrinol (Lausanne). 2022 Dec 23;13:1072647. doi: 10.3389/fendo.2022.1072647. eCollection 2022.

ABSTRACT

BACKGROUND: Mixed pituitary TSH/GH adenomas are rare adenomas associated with acromegaly and/or thyrotoxicosis, with or without varying degrees of goiter. In this report, we show a case of pituitary adenoma producing both GH and TSH simultaneously.

CASE PRESENTATION: A 27-year-old man was diagnosed with pituitary adenoma based on various symptoms and clinical findings. For further examination and treatment, he was hospitalized in our institution. It was likely that this subject had pituitary adenoma producing both GH and TSH. In brain magnetic resonance imaging, there was a giant tumor in the sellar region. After the diagnosis of mixed pituitary TSH/GH adenoma, he was treated with octreotide, then underwent tumor resection, and then received hydrocortisone acetate and levothyroxine sodium. After then, GH and IGF-1 levels were suppressed and thyroid function was normalized. Postoperative immunohistochemistry reports showed GH (+) but TSH (-), which may be insensitive to the antibody used to detect TSH or combined with other factors.

CONCLUSIONS: The diagnosis of mixed pituitary TSH/GH adenoma must be combined with clinical manifestations, immunohistochemical staining and relevant hormone levels, and genetic testing if necessary for comprehensive judgment. For patients with large adenomas, it is recommended to use somatostatin analogs to restore TH levels and control the excessive secretion of GH levels before surgery.

PMID:36619586 | PMC:PMC9816123 | DOI:10.3389/fendo.2022.1072647

Stereotactic radiosurgery for pituitary and cavernous sinus metastases

Fetched: January 9th, 2023, 5:01am GMT by Yen-Yu Lin

J Neurooncol. 2023 Jan 9. doi: 10.1007/s11060-023-04236-3. Online ahead of print.

ABSTRACT

PURPOSE: Metastases extending to the pituitary gland and cavernous sinus are extremely rare; however, advances in neuroimaging have increased the reported incidence. Stereotactic radiosurgery (SRS) affords the precise delivery of focused radiation to minimize adverse radiation effects. This study assessed the efficacy and safety of SRS in the treatment of pituitary and cavernous sinus metastases.

METHODS: Analysis was performed on 23 patients with pituitary and cavernous sinus metastases who underwent treatment using SRS between 1996 and 2021. The cohort was categorized into 2 groups in terms of metastasis location: pituitary involvement (Group 1, n = 11) and cavernous sinus involvement (Group 2, n = 12). Overall survival, local tumor control, and distal tumor control rates were compared between the two groups using Kaplan-Meier analysis.

RESULTS: The median age of the cohort was 52.2 years and the median tumor volume was 4.5 mL. Overall survival rates were as follows: 1 year (72.9%), 2 years (51.8%), and 3 years (45.3%). Local tumor control rates were as follows: 1 year (82.3%), 2 years (82.3%), and 3 years (65.9%). Visual deficit and hypopituitarism were the most common presentations in Group 1, whereas cranial nerve deficit was the most common presentation in Group 2.

CONCLUSIONS: SRS appears to be a safe and effective therapy for the treatment of pituitary and cavernous sinus metastases. GKRS is a relatively simple procedure, which places minimal stress on the patient, thereby facilitating further anti-cancer treatment. Considering the limited survival duration in cases of metastasis, it is very likely that post-GKRS complications (e.g., new onset cranial nerve deficit and hypopituitarism) would not become an issue before patient passes away.

PMID:36617600 | DOI:10.1007/s11060-023-04236-3

Splenic Metastatic Choriocarcinoma with Nontraumatic Splenic Rupture: A Case Report and Literature Review

Fetched: January 9th, 2023, 5:01am GMT by Yifan Chu

J Clin Med. 2022 Dec 25;12(1):157. doi: 10.3390/jcm12010157.

ABSTRACT

Choriocarcinoma is a highly malignant trophoblastic tumor that occurs mostly in women of childbearing age. The main mode of metastasis is hematogenous metastasis. The most common sites of metastasis are the lung, vagina and brain, while splenic metastasis is rare. Because of its rapid development, extensive metastasis can occur in a short period, and some patients only show metastatic symptoms, which are often missed or misdiagnosed as ectopic pregnancy or other diseases. We describe a rare case of splenic metastatic choriocarcinoma with acute abdominal pain caused by nontraumatic splenic rupture. In addition, we review the previous literature on splenic metastasis of choriocarcinoma and summarize the clinical manifestations, management measures and prognoses. Our case and literature review indicate that splenic metastatic choriocarcinoma is rare and difficult to distinguish from splenic ectopic pregnancy and other diseases. Clinicians should strengthen their understanding of this disease and avoid misdiagnosis.

PMID:36614958 | PMC:PMC9821716 | DOI:10.3390/jcm12010157

Spheno-Orbital Meningioma and Vision Impairment-Case Report and Review of the Literature

Fetched: January 9th, 2023, 5:01am GMT by Joanna Wierzbowska

J Clin Med. 2022 Dec 22;12(1):74. doi: 10.3390/jcm12010074.

ABSTRACT

(1) Background: Spheno-orbital meningioma (SOM) is a very rare subtype of meningioma which arises from the sphenoid ridge with an orbital extension. It exhibits intraosseous tumor growth with hyperostosis and a widespread soft-tissue growth at the dura. The intra-orbital invasion results in painless proptosis and slowly progressing visual impairment. (2) Methods: We present a case of a 46-year-old woman with SOM and compressive optic nerve neuropathy related to it. Her corrected distance visual acuity (CDVA) was decreased to 20/100, she had extensive visual field (VF) scotoma, dyschromatopsia, impaired pattern-reversal visual-evoked potential (PVEP), and decreased thicknesses of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), measured with the swept-source optical coherence tomography (SS-OCT), and a pale optic nerve disc in her left eye. Brain CT and MRI showed a lesion at the base of the anterior cranial fossa, involving the sphenoid wing and orbit. Pterional craniotomy and a partial removal of the tumor at the base of the skull and in the left orbit with the resection of the lesional dura mater and bony defect reconstruction were performed. (3) Results: The histological examination revealed meningothelial meningioma (WHO G1). Decreased CDVA and VF defects completely recovered, and the color vision score and PVEP improved following the surgery, but RNFL and GCC remained impaired. No tumor recurrence was observed at a follow-up of 78 months. (4) Conclusions: Optic nerve dysfunction has the capacity to improve once the compression has been relieved despite the presence of the structural features of optic nerve atrophy.

PMID:36614875 | PMC:PMC9821601 | DOI:10.3390/jcm12010074

Fetal Brain Tumors, a Challenge in Prenatal Diagnosis, Counselling, and Therapy

Fetched: January 9th, 2023, 5:01am GMT by Ivonne Alexandra Bedei

J Clin Med. 2022 Dec 21;12(1):58. doi: 10.3390/jcm12010058.

ABSTRACT

Fetal brain tumors are a rare entity with an overall guarded prognosis. About 10% of congenital brain tumors are diagnosed during fetal life. They differ from the postnatally encountered pediatric brain tumors with respect to location and tumor type. Fetal brain tumors can be benign or malignant and infiltrate or displace adjacent brain structures. Due to their high mitotic rate, they can show rapid growth. Outcome depends on age of diagnosis, size, and histological tumor type. Findings like polyhydramnios and macrocephaly encountered on routine ultrasound are frequently associated. Detailed prenatal anomaly scan and subsequent fetal magnetic resonance imaging (MRI) may identify the brain tumor and its severity. Both maternal and fetal prognosis should be included in prenatal counselling and decision making.

PMID:36614855 | PMC:PMC9821081 | DOI:10.3390/jcm12010058

Mutational Analysis of EGFR Mutations in Non-Small Cell Lung Carcinoma-An Indian Perspective of 212 Patients

Fetched: January 9th, 2023, 5:01am GMT by Amrit Kaur Kaler

Int J Environ Res Public Health. 2022 Dec 31;20(1):758. doi: 10.3390/ijerph20010758.

ABSTRACT

Lung cancer is the world's leading cause of cancer-related deaths. Epidermal growth factor receptor (EGFR) is one of the critical oncogenes and plays a significant role in tumor proliferation and metastasis. Patients with sensitizing mutations in the EGFR gene have better clinical outcomes when treated with tyrosine kinase inhibitors (TKI). This study expands our knowledge of the spectrum of EGFR mutations among lung cancer patients in the Indian scenario. This is a retrospective descriptive study of all newly diagnosed patients with lung cancer in tertiary care hospital in India. All the samples were subjected to real-time PCR (q-PCR) analysis and confirmation of rare novel mutations was done using Sanger sequencing. Clinicopathological characteristics, mutational EGFR status, and location on the exon and metastatic sites were evaluated. An analysis of total 212 samples showed mutations in 38.67% of cases. Among these, five (5.9%) samples had mutations in exon 18, 41 (48.8%) samples had mutations in exon 19, 12 (14.28%) samples had mutations in exon 20, and 26 (30.95%) samples had mutations in exon 21. Eleven (13.41%) were found to be uncommon EGFR mutations. Additionally, six (21.4%) samples that had EGFR mutations were also positive for brain metastasis. Future testing on bigger panels will help to characterize the incidence of genetic mutations and to determine the appropriate targeted treatment choices for NSCLC patients.

PMID:36613084 | PMC:PMC9819110 | DOI:10.3390/ijerph20010758

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy

Fetched: January 9th, 2023, 5:01am GMT by Pei-Pei Zhang

Signal Transduct Target Ther. 2023 Jan 6;8(1):24. doi: 10.1038/s41392-022-01291-6.

ABSTRACT

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor β receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.

PMID:36609561 | PMC:PMC9816522 | DOI:10.1038/s41392-022-01291-6

Permalink for 'Weathering the storm: a single-institution experience with paroxysmal sympathetic hyperactivity after brain tumor resection in pediatric patients'

Weathering the storm: a single-institution experience with paroxysmal sympathetic hyperactivity after brain tumor resection in pediatric patients

Fetched: January 9th, 2023, 5:01am GMT by Samantha M Bouchal

J Neurosurg Pediatr. 2023 Jan 6:1-8. doi: 10.3171/2022.12.PEDS22369. Online ahead of print.

ABSTRACT

OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) is a complication of severe traumatic or hypoxic brain injury characterized by transient episodes of tachycardia, tachypnea, hypertension, hyperthermia, diaphoresis, and/or dystonic posturing. Posttraumatic "sympathetic storms" are associated with poor outcomes. PSH rarely occurs after brain tumor resection in pediatric patients; only 4 cases have been published since 1929. Thus, the authors sought to report their experience with postcraniotomy PSH in pediatric brain tumor patients.

METHODS: A retrospective study of patients younger than 18 years of age who underwent craniotomy for brain tumor resection at a single center by a single surgeon over a 7-year period was performed. A clinical diagnosis of postoperative PSH was recorded. Recorded outcomes included the interval between surgery and initiation of cytotoxic therapy, need for long-term CSF diversion, length of hospital stay, and survival.

RESULTS: Of the 150 patients who were included for analysis, 4 patients were diagnosed with postoperative PSH for an overall occurrence of 2.7%. PSH patients were younger than non-PSH patients (1.8 ± 0.4 years vs 9.2 ± 5.3 years, p = 0.010) and tended to have intraventricular tumors close to the thalamus, basal ganglia, and/or brainstem. PSH patients experienced longer hospital admissions (44.3 ± 23.4 days vs 6.8 ± 9.4 days, p = 0.001), a shorter interval between surgery and initiation of cytotoxic cancer-directed therapy (14.3 ± 8.0 days vs 90.7 days ± 232.9 days, p = 0.011), and increased need for long-term CSF diversion compared with non-PSH patients (75% vs 25%, p = 0.005). At the last follow-up, 50% of PSH patients had died compared with 13% of non-PSH patients (p = 0.094).

CONCLUSIONS: PSH is a rare postoperative complication that may affect young children with periventricular tumors and is associated with poorer clinical outcomes. Increasing awareness of this condition is vital to improving patient outcomes.

PMID:36609373 | DOI:10.3171/2022.12.PEDS22369

Glioblastoma in the contralateral cerebral hemisphere with previous surgery for meningioma: A case report

Fetched: January 7th, 2023, 5:01am GMT by Zhe Wang

Medicine (Baltimore). 2023 Jan 6;102(1):e32616. doi: 10.1097/MD.0000000000032616.

ABSTRACT

RATIONALE: Meningioma and glioblastoma (GBM) are 2 common intracranial tumors with different pathophysiologies and prognoses. It is rare for these 2 kinds of tumors to occur in the same patient. Most of the similar cases reported in the literature have been treated with radiotherapy, while cases without radiotherapy are rare. In particular, GBM in the contralateral cerebral hemisphere after resection of meningioma has not been reported.

PATIENT CONCERNS: We present a case of a 66-years-old man with GBM in the right temporal lobe after previous resection of a benign meningioma of the left frontal lobe without radiotherapy.

DIAGNOSES: The patient was admitted to our hospital for the first time because of right upper limb weakness. Brain magnetic resonance imaging indicated a space-occupying lesion in the left frontal area. Surgical treatment was performed, and postoperative pathology confirmed a meningioma. The patient was readmitted to the hospital 3 years after surgery of the meningioma due to a new lesion of the right temporal lobe and underwent reoperation. The postoperative pathological results showed GBM.

INTERVENTIONS: The patient underwent 2 operations, and the postoperative pathologies were meningioma and GBM. In addition, the patient received concurrent chemoradiotherapy and 2 cycles of temozolomide adjuvant chemotherapy.

OUTCOMES: During the last 4 months of follow-up, the patient was in good condition with no recurrence of the tumor.

LESSONS: The development of GBM without radiotherapy after meningioma surgery is very rare, especially at different sites, and it is necessary to accumulate relevant cases to reveal the causes of the disease and provide more evidence for the treatment of similar patients in the future.

PMID:36607853 | PMC:PMC9829253 | DOI:10.1097/MD.0000000000032616

Prognostic value of Ki-67 index in primary intracranial tumors of infants

Fetched: January 7th, 2023, 5:01am GMT by Alican Tahta

Childs Nerv Syst. 2023 Jan 6. doi: 10.1007/s00381-022-05822-y. Online ahead of print.

ABSTRACT

OBJECTIVE: Primary intracranial tumors are rare tumors in infants. They differ from those found in other pediatric age groups in terms of clinical presentation, histopathological diagnosis, adjuvant therapies, and outcome. Ki-67 index has also shown promising results as a prognostic factor in different types of intracranial tumors in children and adults. However, the importance and the best cutoff point of Ki-67 index in primary intracranial tumors of infants remains unclear. We aimed to analyze prognostic value of Ki-67 index in primary intracranial tumors of infants.

METHODS: This study retrospectively reviewed the records of 28 infants undergoing surgical resection for primary intracranial tumors between April 2016 and March 2021. We analyzed clinical characteristics, tumor location, extent of resection, histopathological diagnosis, Ki-67 index, and overall survival (OS). To define the most relevant cutoff value for Ki-67 index, "Cutoff Finder" was used.

RESULTS: The median age at diagnosis was 188 days for all patients. Fifteen of the patients were boys and 13 were girls. Tumors were located supratentorial in 13 patients and infratentorial in 15 patients. Gross total resection was performed in 7 of 13 supratentorial tumors and 9 of 15 infratentorial tumors. The mean Ki-67 index of the supratentorial tumors was 49.6%, the median was 55%; for infratentorial tumors, the mean was 49.9%, and the median was 70%. Tumor grade (p = 0.019) and Ki-67 index (p = 0.003) were found as significant predictors of OS in log-rank testing for Kaplan-Meier survival analysis. Univariate cox regression analysis identified high Ki-67 index as prognostic factor for worse OS, with hazard ratio of 8.852 (95% CI 1.95-64.80; p = 0.0108). High Ki-67 index was found as independent prognostic factor for worse OS in multivariate cox regression analysis (HR 7.036; 95% CI 1.229-65.82; p = 0.0457).

CONCLUSION: High-grade and high Ki-67 index were associated with worse outcome. Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 72.5%.

PMID:36607388 | DOI:10.1007/s00381-022-05822-y

A Case of Infant-Type Hemispheric Glioma with NTRK1 Fusion

Fetched: January 6th, 2023, 5:01am GMT by Mekka R Garcia

Child Neurol Open. 2022 Dec 22;9:2329048X221146982. doi: 10.1177/2329048X221146982. eCollection 2022 Jan-Dec.

ABSTRACT

The incidence of childhood central nervous system tumors in infants is about 6 per 100 000 children. Recent studies have showed recurrent fusion of the neurotrophic tyrosine receptor kinase (NTRK) gene in 10% of non-brainstem high grade glioma in very young children suggesting an oncogenic effect of the NTRK fusion genes. In this report, we present a rare, severe case of a full-term neonate who was noted to have widely splayed sutures and a bulging fontanelle at birth who was found to have infant-type hemispheric glioma with NTRK1 fusion with course complicated by seizures refractory to medical treatment. Patient was deemed a poor surgical candidate due to the size of the mass and thus parents opted for comfort care.

PMID:36601394 | PMC:PMC9806371 | DOI:10.1177/2329048X221146982

Permalink for 'Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component - A case report and review of the literature'

Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component - A case report and review of the literature

Fetched: January 6th, 2023, 5:01am GMT by Gabriele Gaggero

Surg Neurol Int. 2022 Dec 23;13:587. doi: 10.25259/SNI_792_2022. eCollection 2022.

ABSTRACT

BACKGROUND: Oligodendroglioma with ganglioglioma-like maturation is a rare entity not included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. To date, only a few cases were described in the literature. We report a case of this tumor, along with a review of the previous case reports/ series.

CASE DESCRIPTION: A 63-year-old man with a left frontal mass and a 2-month history of seizures underwent surgical resection in our center. Grossly, the specimen appeared as a yellowish mass with prominent hemorrhagic component. Microscopically, the lesion was composed by small round cells often surrounded by a clear halo and, near the hemorrhagic area, by scattered large cuboidal cells with vesicular nuclei and prominent eosinophilic nucleoli. On immunohistochemical stains, both cells components tested positive for ATRX, p53, and GFAP; larger ganglion-like cells showed synaptophysin and chromogranin-A expression. IDH1 codon 132 mutation, 1p-19q-codeletion, and MGMT methylation were observed. Eventually, a diagnosis of oligodendroglioma (the WHO grade II) with ganglioglioma-like maturation was rendered. The patient received adjuvant chemotherapy and is currently alive and asymptomatic.

CONCLUSION: Recognition of ganglioglioma-like maturation in oligodendrogliomas may prevent undertreatment of these neoplasms. To this end, fluorescence in situ hybridization assays are crucial for defining the 1p-19q status.

PMID:36600750 | PMC:PMC9805645 | DOI:10.25259/SNI_792_2022

Permalink for 'Complete response with combined therapy in a patient with brain metastasis from nasopharyngeal carcinoma: case report and literature review'

Complete response with combined therapy in a patient with brain metastasis from nasopharyngeal carcinoma: case report and literature review

Fetched: January 6th, 2023, 5:01am GMT by Liji Jiang

J Int Med Res. 2023 Jan;51(1):3000605221147187. doi: 10.1177/03000605221147187.

ABSTRACT

Brain metastasis of nasopharyngeal carcinoma (NPC) is a rare event with limited research. In this report, we discuss the details of a case of brain metastasis from NPC that presented with a solitary, cystic lesion in the frontal lobe. We also reviewed the related literature published in the last 20 years. We analyzed the patient's clinical characteristics, which indirectly suggested hematogenous spread rather than a cerebrospinal fluid route. Although there are no standard treatments for brain metastasis of NPC, previous studies reported that combined surgery and radiotherapy was a good treatment option, with long survival. Our patient achieved intracranial complete response after the combination of conventional chemoradiotherapy and novel immunotherapy. This treatment option could be useful in future similar cases.

PMID:36597379 | PMC:PMC9830090 | DOI:10.1177/03000605221147187

A case report of epileptic seizures caused by Rosai Dorfman disease followed by a literature review

Fetched: January 6th, 2023, 5:01am GMT by Zhanzhan Zhang

Medicine (Baltimore). 2022 Dec 30;101(52):e32553. doi: 10.1097/MD.0000000000032553.

ABSTRACT

RATIONALE: Rosai Dorfman disease is a rare benign histiocytoproliferative disorder that occurs in the intracranial area, which occurrs typically in lymph nodes. Extrapnodal Rosai Dorfman disease rarely develops in the central nervous system and is often a focal lesion based on the dura. Based on imaging and clinical symptoms, RDD may be misdiagnosed as meningioma, and some lesions can also occur in the brain parenchyma. In the case of benign disease, the final diagnosis is made by pathological tissue diagnosis. For chronic diseases, progression may be chronic or remitting and relapsing.

PATIENT CONCERNS: A 54-years-old man was hospitalized after experiencing paroxic convulsions and being unconsciousness. A head magnetic resonance imaging demonstrates a strip of lesions in the right parietal lobe. No obvious abnormality is found in the laboratory data.

DIAGNOSES: We diagnosed meningioma of right parietal lobe and secondary epilepsy, and prescribed oral sodium valproate to treat him.

INTERVENTIONS: The lesion is located in the right parietal lobe on neuroimaging prior to surgery, which was taken for immunohistochemical examination.

OUTCOMES: If it is found that immunohistochemistry reveals histiocytes are positive for CD68, S-100, but negative for CD1a, it is identified as RDD. For patients who are seizure-free following surgery, symptomatic management is used. Following parietal lesion resection, patients are seizure-free during the follow-up period (44 months).

LESSONS: Basing on studying and summarizing relevant literatures, RDD is described in the report in terms of its diagnosis, pathology, treatment, and clinical outcome, in order to improve the diagnosis and identification of intracranial RDD by physicians.

PMID:36596083 | PMC:PMC9803494 | DOI:10.1097/MD.0000000000032553

Primary meningeal central nervous system lymphoma: A case report and literature review

Fetched: January 6th, 2023, 5:01am GMT by Xue Chen

Medicine (Baltimore). 2022 Dec 30;101(52):e32567. doi: 10.1097/MD.0000000000032567.

ABSTRACT

RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and isolated meningeal PCNSL, without evidence of parenchymal involvement, is even less common, occurring in only 10% to 15% of cases.

PATIENT CONCERNS: A 65-years-old female presented to our hospital with progressive lower extremity motor dysfunction and blurred vision. The initial neurological examination revealed decreased muscle strength in both lower extremities and sensory dysfunction of lower extremities, saddle area, and buttocks. Brain magnetic resonance imaging showed no abnormalities. Lumbar enhanced magnetic resonance imaging showed T11 to L3 horizontal meningeal enhancement. Cerebrospinal fluid (CSF) cytology revealed lymphoma cells. Immunohistochemistry and flow cytometry of the CSF were performed as auxiliary methods to establish the diagnosis of lymphoma.

DIAGNOSES: The patient was diagnosed primary meningeal central nervous system lymphoma.

INTERVENTIONS: During hospitalization, the patient was treated with 2 courses of high-dose intrathecal methotrexate and rituximab combined with intrathecal chemotherapy and supportive treatment.

OUTCOMES: After 2 years of follow-up, the patient was able to walk and take care of herself.

LESSONS: Cases of PCNSL involving only the meninges are rare. Multimodal analysis of the CSF comprises an important component of the diagnostic work-up for patients with primary meningeal central nervous system lymphoma.

PMID:36596043 | PMC:PMC9803511 | DOI:10.1097/MD.0000000000032567

Inflammatory brain lesions preceding primary central nervous system lymphoma: a case report and genetic analysis

Fetched: January 5th, 2023, 5:01am GMT by Zheng XiaoHong

Neurol Sci. 2023 Jan 5. doi: 10.1007/s10072-022-06587-7. Online ahead of print.

ABSTRACT

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal lymphoma exclusively occurring within the central nervous system. Inflammatory brain lesions as "sentinel lesions" of PCNSL are very rare. We present a rare case of PCNSL with preceding inflammatory lesions in an immunocompetent patient who underwent two biopsies, one craniotomy and two genetic testing.

CASE REPORT: A 66-year-old male patient presented with left limb weakness and ataxia. Brain magnetic resonance imaging showed a contrast-enhancing lesion with perifocal brain edema in the near midline of right frontal lobe. Histological examination of a brain biopsy specimen revealed inflammatory lesion characteristics with infiltration of T-cell dominant lymphocytes and few B-cell. Given that the patient developed cerebral hematoma after biopsy, lesion resection by craniotomy was performed. An excised sample demonstrated mixed T-cell and B-cell infiltrating inflammatory lesions. Four months after total resection of the right frontal lobe lesion, another lesion appeared in the left frontal parietal lobe, which was diagnosed as diffuse large B-cell lymphoma by biopsy. In addition, genetic testing of the lesions at two different locations was performed, and the results showed that the inflammatory lesions had the same three gene (RELN, PCLO, and CREBBP) mutations as PCNSL. Interestingly, the three mutated genes are associated with tumor.

CONCLUSION: Our present case is the first to demonstrate inflammatory brain lesions heralding PCNSL from genetic and pathological perspectives. This may help clinicians to select new auxiliary diagnostic methods for timely diagnosis of patients with suspected PCNSL.

PMID:36599976 | DOI:10.1007/s10072-022-06587-7

Confirmation of Intracranial Neuroendocrine Metastasis Utilizing 68Ga-DOTATATE PET/CT

Fetched: January 5th, 2023, 5:01am GMT by Rahim Ismail

J Nucl Med Technol. 2023 Jan 4:jnmt.122.264834. doi: 10.2967/jnmt.122.264834. Online ahead of print.

ABSTRACT

Neuroendocrine tumors (NETs) are rare neoplasms with an exceedingly low incidence of intracranial metastasis. We present a 79-year-old female with a biopsy-proven pulmonary neuroendocrine tumor who presented with an intracranial mass in the posterior fossa that was DOTATATE avid on a ⁶⁸Ga-DOTATATE PET/CT, facilitating the rare diagnosis of intracranial NET metastasis. The case highlights the utility of advanced imaging techniques in differentiating intracranial NET metastasis from other etiologies.

PMID:36599702 | DOI:10.2967/jnmt.122.264834

Global Transient Amnesia as the Predominant Symptom of Cardiac Myxoma: A Case Report

Fetched: January 5th, 2023, 5:01am GMT by Pritee Shrestha

Am J Case Rep. 2023 Jan 3;24:e938221. doi: 10.12659/AJCR.938221.

ABSTRACT

BACKGROUND The most common neurological symptoms from cardiac myxoma-induced stroke include territories of middle cerebral arteries, rendering posterior stroke less common. Although transient global amnesia usually has a benign prognosis, amnesia in the setting of concerning cerebellar symptoms should raise the suspicion for posterior circulation involvement. These benign-appearing symptoms can be manifestations of an acute cerebrovascular accident (CVA). This unusual presentation can delay workup for underlying pathology. CASE REPORT A 67-year-old woman presented to the local emergency department after an episode of global amnesia that lasted about 15 minutes and was associated with some dizziness. The patient also reported a history of chronic disequilibrium. The head CT scan was negative for any acute findings. A follow-up MRI of the brain demonstrated acute small lacunar infarcts within the left cerebellum and right parietal lobe. An echocardiogram was performed due to concern for the cardioembolic source, which revealed left atrial myxoma. She was transferred to a tertiary center for immediate surgical intervention due to the high risk of embolization associated with the condition. The patient subsequently underwent successful surgical excision of the lesion. CONCLUSIONS Cardiac myxoma, although a rare cause of posterior stroke, needs prompt intervention as it is associated with a high risk of systemic embolization, including recurrent CVA. Transient global amnesia is an atypical presentation of cardiac myxoma that can easily be overlooked, delaying timely diagnosis and prompt intervention. Early recognition and surgical resection are crucial to prevent potentially life-threatening consequences.

PMID:36593745 | DOI:10.12659/AJCR.938221

Permalink for 'TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy'

TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy

Fetched: January 4th, 2023, 5:01am GMT by Teresa Rubio

Neurobiol Dis. 2023 Jan;176:105964. doi: 10.1016/j.nbd.2022.105964. Epub 2022 Dec 14.

ABSTRACT

Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy (prevalence <1:1,000,000) characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies, in the brain but also in peripheral tissues. LD is the most severe form of the group of progressive myoclonus epilepsies, since patients present a rapid deterioration and dementia with amplification of seizures, leading to death after a decade from the onset of the first symptoms. We have recently described that reactive glia-derived neuroinflammation should be considered a novel hallmark of LD since we observed a florid upregulation of differentially expressed genes in both LD mouse lines, which were mainly related to mediators of inflammatory response. In this work, we define an upregulation of the expression of mediators of the TNF and IL6/JAK2 signaling pathways in LD. In addition, we describe the activation of the non-canonical form of the inflammasome. Furthermore, we describe the infiltration of peripheral immune cells in the brain parenchyma, which could aggravate glia-derived neuroinflammation. Finally, we describe CXCL10 and S100b as blood biomarkers of the disease, which will allow the study of the progression of the disease using serum blood samples. We consider that the identification of these initial inflammatory changes in LD will be very important to implement possible anti-inflammatory therapeutic strategies to prevent the development of the disease.

PMID:36526090 | DOI:10.1016/j.nbd.2022.105964

Primary intraosseous alveolar soft part sarcoma: Report of two cases with radiologic-pathologic correlation

Fetched: January 4th, 2023, 5:01am GMT by E M Pena-Burgos

Ann Diagn Pathol. 2023 Feb;62:152078. doi: 10.1016/j.anndiagpath.2022.152078. Epub 2022 Dec 13.

ABSTRACT

Alveolar soft part sarcoma (ASPS) accounts for less than 1 % of all soft tissue sarcomas. ASPS presents a poor prognosis and develops frequent metastases, especially in the lungs, brain and bones. Current therapies, such as surgery, radiotherapy and chemotherapy, are not fully effective and other alternative treatments are currently being studied. ASPS is predominantly found in the deep soft tissues of the lower extremities. To our knowledge, only thirteen primary intraosseous ASPS have been reported in the literature. In this study, we report two new cases of this exceedingly rare entity. Both cases already had multiple metastases since diagnosis; one of them represents the first case of a primary bone ASPS in the ulna and is also the primary intraosseous ASPS with the longest reported case of survival, after having maintained long periods of stabilization despite not having received any systemic treatment.

PMID:36543620 | DOI:10.1016/j.anndiagpath.2022.152078

Signaling pathways in brain tumors and therapeutic interventions

Fetched: January 4th, 2023, 5:01am GMT by Shenglan Li

Signal Transduct Target Ther. 2023 Jan 4;8(1):8. doi: 10.1038/s41392-022-01260-z.

ABSTRACT

Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain tumors, enhanced biological understanding and unexampled innovations in targeted therapies and immunotherapies have considerably improved patients' prognoses. Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. Previous literature data revealed that several different signaling pathways are dysregulated in brain tumor. Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. This paper began with a brief description of the epidemiology, incidence, risk factors, as well as survival of brain tumors. Next, the major signaling pathways underlying these brain tumors' pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed. Finally, future perspective and challenges of development of novel therapeutic strategies in brain tumor were emphasized.

PMID:36596785 | PMC:PMC9810702 | DOI:10.1038/s41392-022-01260-z

MRI Finding of Residual Tumor of Giant Oligodendroglioma in Pediatric: A Case Report

Fetched: January 4th, 2023, 5:01am GMT by Gustiara Munir

Radiol Case Rep. 2022 Dec 23;18(3):907-912. doi: 10.1016/j.radcr.2022.11.059. eCollection 2023 Mar.

ABSTRACT

Oligodendroglioma is a rare brain tumor. Although it commonly originates in the cerebral hemisphere in adults, in the pediatric population, the location of oligodendroglioma varies and includes the cerebellum, midbrain, and spinal cord. The MRI characteristic of oligodendroglioma is also different between adults and pediatrics. Oligodendroglioma of >3 cm in pediatrics is associated with a poorer prognosis. Surgery and radiotherapy are the modality of choice for such patients. In this case, we present a 12-year-old girl with huge oligodendroglioma (WHO grade II). MRI showed an isointense-inhomogeneous signal on T1W1 and isointense with some region of hyperintense inhomogeneous on T2W1. After a 26-times-radiotherapy regimen, the patient was followed up for MRI evaluation and which revealed a marked reduction of tumor volume. The patient also reported no symptoms and overall clinical improvement.

PMID:36593920 | PMC:PMC9803691 | DOI:10.1016/j.radcr.2022.11.059

Pathological Significance of Kidney and Brain Expressed Protein (KIBRA) in Clear Cell Renal Cell Carcinoma

Fetched: January 4th, 2023, 5:01am GMT by Yoshiaki Nagashima

Anticancer Res. 2023 Jan;43(1):45-51. doi: 10.21873/anticanres.16132.

ABSTRACT

BACKGROUND/AIM: Kidney and brain expressed protein (KIBRA), a member of the WW domain-containing protein family, has an important role in tumour growth and progression in various cancers. However, the pathological significance of KIBRA expression in clear cell renal cell carcinoma (ccRCC) tissues is not fully understood. The aim of this study was to clarify the pathological significance and prognostic roles of KIBRA expression in patients with ccRCC.

MATERIALS AND METHODS: KIBRA immunoreactivity, proliferation index (PI; with anti-Ki-67 antibody), apoptotic index (AI; using anti-cleaved caspase-3), and large tumour suppressor kinases (LATS-2) were evaluated in 157 ccRCC specimens by immunohistochemistry. Fifty normal kidney tissues were also evaluated as controls. The relationships between KIBRA expression and these cancer-related variables as well as clinicopathological features and survival were analysed.

RESULTS: Moderate to strong immunoreactivity of KIBRA was identified in all normal kidney tissues; however, ccRCC cells with strong KIBRA expression was rare. The immunoreactivity score (IRS) of KIBRA was negatively associated with grade, T stage, tumour diameter, and metastasis. Kaplan-Meier survival curves showed that high KIBRA expression was a favourite predictor for overall survival. KIBRA IRS was negatively associated with PI and positively associated with the IRS of LATS-2 by univariate analysis. In addition, multivariate analysis showed that KIBRA was significantly associated with PI.

CONCLUSION: KIBRA demonstrated important roles as a tumour suppressor in ccRCC. In addition, its expression was significantly associated with survival in these patients. Several such KIBRA-related functions were speculated to be modulated by cancer cell proliferation and LATS-2.

PMID:36585159 | DOI:10.21873/anticanres.16132

Cerebral developmental venous anomalies in children with mismatch repair deficiency

Fetched: January 4th, 2023, 5:01am GMT by Buket Kara

Turk J Pediatr. 2022;64(6):1106-1116. doi: 10.24953/turkjped.2021.3921.

ABSTRACT

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is one of the rare cancer predisposition syndromes. The aim of this study was to evaluate the cerebral developmental venous anomalies in children with central nervous system tumors associated with CMMRD, an area in which there is extremely little experience.

METHODS: Data from children diagnosed with medulloblastoma and high grade central nervous sytem tumor were retrospectively collected. According to the European CMMRD criteria, nine patients were diagnosed as CMMRD syndrome and the others consisted of the group without CMMRD. All radiological examinations of these children were retrospectively reviewed. Whole exome sequencing was performed to index cases` germline DNA.

RESULTS: Nine children from four families, six females and three males, were studied. The median age at the first tumor diagnosis was 4.5 years (range, 9 months to 14 years). All CMMRD patients had café au lait spots, but none fulfilled the diagnostic criteria for neurofibromatosis. The patients developed high-grade glial tumor (n: 7) and medulloblastoma (n: 2). The affected genes in the three families were MSH6 [c.478C > T (p.Gln160Ter)], MSH6 [c.2871dupC (p.Phe958LeufsTer5)] and MLH1 [c.236G > A(p.Arg79Lys)], respectively. Seven patients had multiple developmental venous anomalies; six patients had leptomeningeal enhancement; and five patients had cavernomas. None of these findings were present in the group without CMMRD.

CONCLUSIONS: Constitutional mismatch repair deficiency should be considered when multiple developmental venous anomalies, cavernomas, and leptomeningeal enhancement are detected, especially in patients with café au lait spots.

PMID:36583892 | DOI:10.24953/turkjped.2021.3921

Permalink for 'An open-label multi-center phase 1 safety study of BXQ-350 in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors'

An open-label multi-center phase 1 safety study of BXQ-350 in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors

Fetched: January 3rd, 2023, 5:01am GMT by Mohamed S Abdelbaki

Heliyon. 2022 Dec 19;8(12):e12450. doi: 10.1016/j.heliyon.2022.e12450. eCollection 2022 Dec.

ABSTRACT

BACKGROUND: BXQ-350 is a novel anti-neoplastic agent composed of saposin C (SapC) and phospholipid dioleoylphosphatidyl-serine sodium (DOPS) that selectively binds tumor cell phosphatidylserine (PS), inducing apoptosis. BXQ-350 has demonstrated preclinical antitumor effects in high-grade gliomas (HGG) and clinical activity in adult patients with recurrent HGG.

METHODS: A phase 1 study was conducted in pediatric patients with relapsed/refractory solid tumors, including recurrent brain tumors. Primary objectives were to characterize safety and determine maximum tolerated dose (MTD) and preliminary antitumor activity. Sequential dose cohorts were assessed up to 3.2 mg/kg using an accelerated titration design. Each cycle was 28 days; dosing occurred on days 1-5, 8, 10, 12, 15, and 22 of cycle 1, and day 1 of subsequent cycles, until disease progression or toxicity.

RESULTS: Nine patients, median age 10 years (range: 4-23), were enrolled. Seven patients (78%) had central nervous system (CNS) and two (22%) had non-CNS tumors. Eight patients completed cycle 1. No dose limiting toxicity (DLT) or BXQ-350-related serious adverse events (SAEs) were observed. Six patients experienced at least one adverse event (AE) considered possibly BXQ-350-related, most were grade ≤2. One patient with diffuse intrinsic pontine glioma experienced stable disease for 5 cycles. The study was terminated after part 1 to focus development on the frontline setting.

CONCLUSION: No DLTs or BXQ-350-related SAEs were reported, and the maximal planned dose of 3.2 mg/kg IV was tolerable. Limited safety and efficacy data support continued BXQ-350 development in pediatric HGG; however, early discontinuations for progression suggest novel therapies be assessed at earlier disease stages.

PMID:36590576 | PMC:PMC9798181 | DOI:10.1016/j.heliyon.2022.e12450

Permalink for 'Constitutional microsatellite instability, genotype, and phenotype correlations in Constitutional Mismatch Repair Deficiency'

Constitutional microsatellite instability, genotype, and phenotype correlations in Constitutional Mismatch Repair Deficiency

Fetched: January 2nd, 2023, 5:01am GMT by Richard Gallon

Gastroenterology. 2022 Dec 28:S0016-5085(22)01444-5. doi: 10.1053/j.gastro.2022.12.017. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Constitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline mismatch repair (MMR) variants. Constitutional microsatellite instability (cMSI) is a CMMRD diagnostic hallmark and may associate with cancer risk. We quantified cMSI in a large CMMRD patient cohort to explore genotype-phenotype correlations, using novel MSI markers selected for instability in blood.

METHODS: Three CMMRD, one Lynch syndrome (LS), and two control blood samples were genome sequenced to >120x depth. A pilot cohort of eight CMMRD and 38 control blood samples, and a blinded cohort of 56 CMMRD, eight suspected CMMRD, 40 LS, and 43 control blood samples were amplicon sequenced to 5000x depth. Sample cMSI score was calculated using a published method comparing microsatellite reference allele frequencies to 80 controls.

RESULTS: Thirty-two mononucleotide repeats were selected from blood genome and pilot amplicon sequencing data. cMSI scoring using these MSI markers achieved 100% sensitivity (95% CI: 93.6-100.0%) and specificity (95% CI: 97.9-100.0%), was reproducible, and was superior to an established tumour MSI marker panel. Lower cMSI scores were found in CMMRD patients with MSH6 deficiency and patients with at least one MMR missense variant, whilst patients with biallelic truncating/copy number variants had higher scores. cMSI score did not correlate with age at first tumour.

CONCLUSIONS: We present a cheap and scalable cMSI assay that enhances CMMRD detection relative to existing methods. cMSI score is associated with MMR genotype but not phenotype, suggesting it is not a useful predictor of cancer risk.

PMID:36586540 | DOI:10.1053/j.gastro.2022.12.017

Collision of Two Tumors: A Case Report of a Lung Adenocarcinoma With Metastasis to a Pituitary Adenoma

Fetched: December 31st, 2022, 5:01am GMT by Marisa Khatijah Borhan

J ASEAN Fed Endocr Soc. 2022;37(2):89-94. doi: 10.15605/jafes.037.02.09. Epub 2022 Jun 16.

ABSTRACT

A collision tumor involving metastasis to a pituitary adenoma is rare. We describe a case of a 68-year-old Bidayuh woman with underlying treatment-responsive lung adenocarcinoma, who presented with mass effect, panhypopituitarism and polyuria. Her initial imaging study reported pituitary macroadenoma, and she was treated with hormone replacement therapy. She then underwent transsphenoidal tumor debulking surgery with subsequent histopathological findings of a collision tumor of an adenocarcinoma with metastasis to a non-functioning pituitary adenoma.

PMID:36578883 | PMC:PMC9758545 | DOI:10.15605/jafes.037.02.09

Primary central nervous system CD20-negative diffuse large B-cell lymphoma: a case report

Fetched: December 30th, 2022, 5:01am GMT by Shuai Luo

BMC Neurol. 2022 Dec 29;22(1):504. doi: 10.1186/s12883-022-03031-3.

ABSTRACT

BACKGROUND: CD20-negative diffuse large B-cell lymphoma is a very rare and heterogeneous invasive cancer characterized by chemical resistance and poor prognosis. Primary CD20-negative diffuse large B-cell lymphoma of the central nervous system is even rarer, presenting great challenges in pathological diagnosis and clinical treatment.

CASE PRESENTATION: We report a case of primary CD20-negative diffuse large B-cell lymphoma of the CNS in a 54-year-old woman admitted to the hospital with a headache lasting more than 10 days. CT and MRI scans showed right temporal lobe lymphoma. Microscopically, large infiltrating lymphoid cells that induced brain tissue damage were observed. Immunohistochemistry showed that the tumor cells were CD79a⁺, PAX-5⁺, MUM1⁺, and CD20^-. The patient was diagnosed with lymphoma and transferred to an oncology hospital for chemotherapy. However, because the disease progressed rapidly, the patient died only after two rounds of chemotherapy.

CONCLUSIONS: To the best of our knowledge, this is one of the first reported cases of unclassifiable CD20-negative diffuse large B-cell lymphoma located in the CNS. This case report aims to deepen the understanding of clinicopathological features of this type of lymphoma and expand the scope of this disease.

PMID:36581860 | PMC:PMC9798623 | DOI:10.1186/s12883-022-03031-3

Permalink for 'Arteriolosclerosis differs from venular collagenosis in relation to cerebrovascular parenchymal damages: an autopsy-based study'

Arteriolosclerosis differs from venular collagenosis in relation to cerebrovascular parenchymal damages: an autopsy-based study

Fetched: December 30th, 2022, 5:01am GMT by Yuan Cao

Stroke Vasc Neurol. 2022 Dec 29:svn-2022-001924. doi: 10.1136/svn-2022-001924. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations.

METHODS: We evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed.

RESULTS: Arteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (β=-0.430, p=0.028) and deep white matter (β=-0.437, p=0.025).

CONCLUSION: Our findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.

PMID:36581493 | DOI:10.1136/svn-2022-001924

Use of optical coherence tomography in diagnosis of retinal lymphomas

Fetched: December 30th, 2022, 5:01am GMT by O F Tropinskaya

Vestn Oftalmol. 2022;138(6):14-19. doi: 10.17116/oftalma202213806114.

ABSTRACT

Primary intraocular lymphomas (PIOL) affecting the vitreoretinal complex is a rare nosology, and because of that PIOLs often cause diagnostic difficulties and/or lead to misdiagnosis. In the event of retinal lesions, in addition to routine ophthalmoscopy, optical coherence tomography (OCT) of the retina plays an important role in the diagnosis of the disease.

PURPOSE: Evaluation of the characteristic features of retinal lymphomas using OCT.

MATERIAL AND METHODS: The study included 6 patients (10 eyes) with retinal lymphomas associated with brain lesions of diffuse large B-cell lymphoma (DLBCL) who were treated at the N.N. Burdenko National Medical Research Center of Neurosurgery from 2017 to 2020; they were examined with OCT.

RESULTS: All patients with retinal lymphomas showed typical OCT signs in the form of hyperreflective subretinal infiltrates.

CONCLUSION: OCT is a modern non-invasive method that allows diagnosing retinal lymphomas based on clinical and instrumental signs with a high degree of reliability.

PMID:36573943 | DOI:10.17116/oftalma202213806114

Craniocerebral Maduramycosis: Masquerading as a Tumor

Fetched: December 27th, 2022, 5:01am GMT by Inuganti Venkata Renuka

Asian J Neurosurg. 2022 Dec 14;17(4):635-637. doi: 10.1055/s-0042-1757627. eCollection 2022 Dec.

ABSTRACT

Eumycetomas of craniocerebral are rare, and we report an extraordinary case of maduramycosis involving brain and skull bone in a middle-aged male who presented with complaints of headache, behavioral abnormalities, and memory disturbances for 3 months. Imaging showed a frontal lesion. It was mistaken for a tumor clinically and radiologically. Craniocerebral eumycetoma usually presents as a mass on the scalp with sinuses. Our case presented as a brain tumor without a soft tissue mass or discharging sinuses. It is essential to keep in mind this mode of presentation, and only a biopsy will aid in diagnosis.

PMID:36570760 | PMC:PMC9771607 | DOI:10.1055/s-0042-1757627

Suprasellar Ganglioglioma Arising from the Third Ventricle Floor: A Case Report and Review of the Literature

Fetched: December 27th, 2022, 5:01am GMT by Shaoguang Li

Tomography. 2022 Nov 28;8(6):2844-2853. doi: 10.3390/tomography8060238.

ABSTRACT

Gangliogliomas are uncommon intracranial tumors that include neoplastic and abnormal ganglion cells, and show positive immunohistochemical staining for GFAP and syn. This type of lesion occurs more frequently in the temporal lobe than in other areas; they are extremely rare in the suprasellar region. To the best of our knowledge, including our case, 19 cases of GGs have been found in the suprasellar region. Among them, five tumors invaded the optic nerve, nine tumors invaded the optic chiasm, one tumor invaded the optic tract, and two tumors invaded the entire optic chiasmal hypothalamic pathway. In the present study, we describe the first case of suprasellar GGs arising from the third ventricle floor that was removed through the endoscopic endonasal approach. In addition, we summarize the clinical characteristics of GGs, such as age of onset, gender distribution, MRI signs, main clinical symptoms, and treatment methods for GG cases.

PMID:36548530 | PMC:PMC9788206 | DOI:10.3390/tomography8060238

Permalink for 'Intestinal Mucosa-Associated Lymphoid Tissue Lymphoma Transforming into Diffuse Large B-Cell Lymphoma in a Young Adult Patient with Neurofibromatosis Type 1: A Case Report'

Intestinal Mucosa-Associated Lymphoid Tissue Lymphoma Transforming into Diffuse Large B-Cell Lymphoma in a Young Adult Patient with Neurofibromatosis Type 1: A Case Report

Fetched: December 24th, 2022, 5:01am GMT by Hideki Kosako

Medicina (Kaunas). 2022 Dec 12;58(12):1830. doi: 10.3390/medicina58121830.

ABSTRACT

Background: Neurofibromatosis type 1 (NF1) is a hereditary cancer syndrome characterized by multiple café-au-lait macules on the skin. Lymphoproliferative malignancies associated with NF1 are limited, although the most common are brain tumors. Case presentation: A 22-year-old woman with NF1 was admitted due to abdominal pain and bloody diarrhea. Her laboratory data exhibited macrocytic anemia and elevated IgA levels. Image studies showed diffuse increased wall thickening in the transverse and descending colon without lymphadenopathy and hepatosplenomegaly. A colonoscopy revealed a hemorrhagic ulcerated mass. Pathological analysis of the tumor tissues confirmed IgA-expressing mucosa-associated lymphoid tissue (MALT) lymphoma with histological transformation. Moreover, whole-exome sequencing in tumor tissues and peripheral blood mononuclear cells identified a somatic frameshift mutation of the A20 gene, which represents the loss of function. The patient responded well to R-CHOP chemotherapy, but the disease relapsed after 1 year, resulting in a lethal outcome. Conclusions: MALT lymphoma in children and young adults is extremely rare and is possibly caused by acquired genetic changes. This case suggests a novel association between hereditary cancer syndrome and early-onset MALT lymphoma.

PMID:36557032 | PMC:PMC9782547 | DOI:10.3390/medicina58121830

Insights on Lipomatosis after Platinum-Based Chemotherapy Use in Pediatric Oncology: A Case Report

Fetched: December 24th, 2022, 5:01am GMT by Estera Boeriu

Medicina (Kaunas). 2022 Nov 23;58(12):1715. doi: 10.3390/medicina58121715.

ABSTRACT

Agents of platinum-based chemotherapy, such as cisplatin or carboplatin, are used in the treatment of a wide range of malignancies that affect children, such as brain tumors, osteosarcoma, neuroblastoma, hepatoblastoma, and germ cell tumors (GCTs). The Cyclophosphamide Equivalent Dose (CED) calculator for reproductive risk does not take platinum-based chemotherapy into account, despite the fact that it accounts for the majority of chemotherapy medications that are typically administered for pediatric GCTs. As a result, exposure to platinum-based drugs throughout infancy can have predictable long-term effects such as infertility, as well as other rare encounters such as lipoma formation and lipomatosis. Lipomas are the most prevalent benign soft tissue tumor subtype. They may be either solitary entities or engaged in multiple lipomatosis, which may have a familial origin or be an acquired disorder. Chemotherapy is a possible cause of lipomatosis. Chemotherapy based on cisplatin has been linked to a variety of long-term consequences, including kidney damage, neurotoxicity, and pulmonary toxicity, and may even create secondary cancers. However, lipoma development is known to occur in fewer than 1 in 100 individuals, and only a few examples of multiple cutaneous lipomatosis triggered by this therapy have been documented. Here we present a very rare case of lipomatosis in a pediatric patient with GCT under cisplatin therapy, which might be the third report of this kind affecting children.

PMID:36556917 | PMC:PMC9784424 | DOI:10.3390/medicina58121715

Permalink for 'Overview on Common Genes Involved in the Onset of Glioma and on the Role of Migraine as Risk Factor: Predictive Biomarkers or Therapeutic Targets?'

Overview on Common Genes Involved in the Onset of Glioma and on the Role of Migraine as Risk Factor: Predictive Biomarkers or Therapeutic Targets?

Fetched: December 24th, 2022, 5:01am GMT by Giovanna Casili

J Pers Med. 2022 Nov 28;12(12):1969. doi: 10.3390/jpm12121969.

ABSTRACT

Gliomas are relatively rare but fatal cancers, and there has been insufficient research to specifically evaluate the role of headache as a risk factor. Nowadays, gliomas are difficult to cure due to the infiltrative nature and the absence of specific adjuvant therapies. Until now, mutations in hundreds of genes have been identified in gliomas and most relevant discoveries showed specific genes alterations related to migraine as potential risk factors for brain tumor onset. Prognostic biomarkers are required at the time of diagnosis to better adapt therapies for cancer patients. In this review, we aimed to highlight the significant modulation of CLOCK, BMLA1 and NOTCH genes in glioma onset and development, praising these genes to be good as potentially attractive therapeutic markers for brain tumors. A improved knowledge regarding the role of these genes in triggering or modulating glioma maybe the key to early diagnosing brain tumor onset in patients affected by a simple headache. In addition, investigating on these genes we can suggest potential therapeutic targets for treating brain tumors. These considerations open up the possibility of personalized treatments that can target each brain tumor's specific genetic abnormality.

PMID:36556190 | PMC:PMC9786313 | DOI:10.3390/jpm12121969

T-Cell Mediated Immunity in Merkel Cell Carcinoma

Fetched: December 24th, 2022, 5:01am GMT by Kelsey Ouyang

Cancers (Basel). 2022 Dec 9;14(24):6058. doi: 10.3390/cancers14246058.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4⁺, CD8⁺, and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed.

PMID:36551547 | PMC:PMC9775569 | DOI:10.3390/cancers14246058

Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma

Fetched: December 24th, 2022, 5:01am GMT by Mei Tang

Biomolecules. 2022 Nov 24;12(12):1744. doi: 10.3390/biom12121744.

ABSTRACT

A craniopharyngioma (CP) is a rare epithelial tumor of the sellar and parasellar region. CPs are difficult to treat due to their anatomical proximity to critical nervous structures, which limits the ability of the surgeon to completely resect the lesion, exposing patients to a high risk of recurrence. The treatment of craniopharyngiomas is primarily surgery and radiotherapy. So far, neither a cell line nor an animal model has been established, and thus data on other treatment options, such as chemotherapy and immunotherapy, are limited. Here, the expression profile of the pan-cancer antigen B7-H3 in various cancer types including CP was examined by immunohistochemistry. An in vitro organoid model was established by using fresh tissue biospecimens of CP. Based on the organoid model, we evaluated the antitumor efficacy of B7-H3-targeted immunotherapy on CP. As a result, the highest expression of B7-H3 was observed in CP tissues across various cancer types. Although B7-H3-targeted chimeric antigen-receptor T cells show obvious tumor-killing effects in the traditional 2D cell culture model, limited antitumor effects were observed in the 3D organoid model. The B7-H3-targeted antibody-DM1 conjugate exhibited a potent tumor suppression function both in 2D and 3D models. In conclusion, for the first time, we established an organoid model for CP and our results support that B7-H3 might serve as a promising target for antibody-drug conjugate therapy against craniopharyngioma.

PMID:36551172 | PMC:PMC9775874 | DOI:10.3390/biom12121744

Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review

Fetched: December 23rd, 2022, 5:01am GMT by Wonsuk Yoo

BMC Med Res Methodol. 2022 Dec 22;22(1):327. doi: 10.1186/s12874-022-01810-7.

ABSTRACT

BACKGROUND: Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials.

METHODS: We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. The followings were key words for the literature search as index terms or free-text words: "phase II trials", "glioblastoma", and "two-stage design". We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status.

RESULTS: Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Most trials (90%) used Simon's two-stage designs. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy.

CONCLUSIONS: Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials.

PMID:36550391 | PMC:PMC9773486 | DOI:10.1186/s12874-022-01810-7

Permalink for 'Correlation of MTAP immunohistochemical deficiency with CDKN2A homozygous deletion and clinicopathological features in pleomorphic xanthoastrocytoma'

Correlation of MTAP immunohistochemical deficiency with CDKN2A homozygous deletion and clinicopathological features in pleomorphic xanthoastrocytoma

Fetched: December 23rd, 2022, 5:01am GMT by Lei Lou

Brain Tumor Pathol. 2023 Jan;40(1):15-25. doi: 10.1007/s10014-022-00447-0. Epub 2022 Dec 22.

ABSTRACT

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor ranging from World Health Organization (WHO) grades 2-3 and can potentially recur and metastasize throughout the central nervous system (CNS). Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion is a frequent genomic alteration of PXA. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in PXA. Therefore, we performed CDKN2A fluorescence in situ hybridization and MTAP immunohistochemistry on specimens from 23 patients with CNS WHO grades 2 (n = 10) and 3 (n = 13) PXAs, including specimens from primary and recurrent tumors, and determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 30% (3/10) and 76.9% (10/13) of CNS WHO grades 2 and 3 PXAs, respectively. In addition, MTAP loss was inconsistent with CDKN2A homozygous deletion (sensitivity = 86.7%, specificity = 100%). Furthermore, CDKN2A homozygous deletion was correlated with WHO grade (p = 0.026) and the Ki-67 labeling index (p = 0.037). Therefore, MTAP immunostaining can be a suitable surrogate marker for CDKN2A homozygous deletions in PXAs, and CDKN2A homozygous deletions may be an important prognostic factor for PXAs.

PMID:36550382 | DOI:10.1007/s10014-022-00447-0

Permalink for 'Pleiomorphism plurihormonal Pit-1-positive macroadenoma with central hyperthyroidism: a rare case report and literature review'

Pleiomorphism plurihormonal Pit-1-positive macroadenoma with central hyperthyroidism: a rare case report and literature review

Fetched: December 23rd, 2022, 5:01am GMT by Guiliang Peng

BMC Endocr Disord. 2022 Dec 21;22(1):325. doi: 10.1186/s12902-022-01220-2.

ABSTRACT

BACKGROUND: Thyrotropin-secreting pituitary neuroendocrine tumors (PitNETs) are rare pituitary adenomas that are occasionally accompanied by hypersecretion of other anterior pituitary hormones, such as growth hormone (GH) and prolactin (PRL). The clinical, biochemical, and pathological characteristics may represent diverse circumstances.

CASE PRESENTATION: In this report, a 33-year-old female diagnosed with a TSH PitNET co-secreting GH presented no obvious clinical symptoms. The main characteristics were elevated thyroid-stimulating hormone (TSH), free tri-iodothyronine (FT3), and free thyroxine (FT4) levels accompanied by slightly elevated GH and insulin-like growth factor-1 (IGF-1) levels. Magnetic resonance imaging (MRI) detected a pituitary macroadenoma (18 × 16 × 16 mm) with cavernous sinus and suprasellar invasion. Immunohistochemistry revealed diffuse positivity for TSH, strong immunoreactivity for GH, and sporadic positivity for PRL. The electron microscope and double immunofluorescence staining confirmed a plurimorphous plurihormonal adenoma producing TSH, GH, and PRL. After preoperative somatostatin receptor ligand (SRL) treatment and transsphenoidal surgery, the patient achieved temporary clinical and biochemical remission. However, 3 months after surgery, the patient was suspected of having Hashimoto's thyroiditis due to higher thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), and thyroid receptor antibody (TRAb) and an enlarged thyroid nodule. During follow-up, thyroid function and TSH slowly transformed from transient hyperthyroidism to hypothyroidism. They were maintained in the normal range by L-T4.

CONCLUSION: In the TSH PitNET, the positive immunohistochemistry for TSH, GH, and PRL translated into hormonal overproduction with TSH and GH.

PMID:36539773 | PMC:PMC9769035 | DOI:10.1186/s12902-022-01220-2

Masson Tumor of the Central Nervous System: A Case Report and Review of Literature

Fetched: December 22nd, 2022, 5:01am GMT by Fatemeh Mohammadyari

Am J Case Rep. 2022 Dec 21;23:e937597. doi: 10.12659/AJCR.937597.

ABSTRACT

BACKGROUND Masson's tumor, also known as intravascular papillary endothelial hyperplasia (IPEH), is an unusual endothelial proliferation that leads to improper thrombus development due to faulty endothelial structure. Although IPEH is rare in the central nervous system, it can arise at any location in the brain. Headaches, seizures, and focal neurological symptoms ae the most common presenting symptoms. It is more common in females and it can occur at any age. CASE REPORT Herein, we present a 65-year-old female patient with a progressively enlarging right temporal lobe mass that was initially considered metastatic ovarian carcinoma. She underwent a right temporal craniotomy and the lesion was totally resected. Contrary to expectations, the pathology report was an IPEH. CONCLUSIONS In this paper, we conducted a literature review of previously reported cerebral IPEH cases, with a focus on their clinical and radiological presentations, management, and especially their association with previous radiotherapy. The important point is that one-third of the cases had a history of radiation therapy to the head, and most of them had stereotactic radiosurgery (SRS) on the location of the brain from which IPEH subsequently developed. The major question for which we are looking for an answer is its relationship with previous radiotherapies. We wanted to know how many of these cases were associated with radiotherapy in the same area, the time interval from radiotherapy to the onset of IPEH or symptoms, the dose of the previous radiotherapy, and, overall, if there is any cause-effect relationship between IPEH and radiotherapy.

PMID:36540012 | PMC:PMC9793341 | DOI:10.12659/AJCR.937597

Multiple gliomas

Fetched: December 22nd, 2022, 5:01am GMT by M V Ryzhova

Zh Vopr Neirokhir Im N N Burdenko. 2022;86(6):66-75. doi: 10.17116/neiro20228606166.

ABSTRACT

The authors present 2 patients. One of them had typical multifocal primary multiple synchronous wild-type IDH1/2 glioblastoma subtype RTK1, chromosome 7 duplication, homozygous CDKN2A deletion and chromosome 10 deletion. In another patient, the nature of tumors remains debatable. We can talk about either a rare atypical case of metachronous multicentric various glial tumors (oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, WHO grade 2 and RTK2-glioblastoma) or secondary glioblastoma after previous oligodendroglioma arose a year after radiotherapy.

PMID:36534626 | DOI:10.17116/neiro20228606166

IDH-mutant brainstem glioma

Fetched: December 22nd, 2022, 5:01am GMT by M V Ryzhova

Zh Vopr Neirokhir Im N N Burdenko. 2022;86(6):52-57. doi: 10.17116/neiro20228606152.

ABSTRACT

Diffuse midline gliomas are relatively rare in adults. Regardless of age, all diffuse midline gliomas are routinely examined in our Center for the presence of the H3F3A K27M gene mutation. However, we identified IDH-mutant brainstem glioma in a 42-year-old man for the first time.

PMID:36534624 | DOI:10.17116/neiro20228606152

Permalink for 'ALT in Pediatric High-Grade Gliomas Can Occur without ATRX Mutation and is Enriched in Patients with Pathogenic Germline MMR Variants'

ALT in Pediatric High-Grade Gliomas Can Occur without ATRX Mutation and is Enriched in Patients with Pathogenic Germline MMR Variants

Fetched: December 22nd, 2022, 5:01am GMT by Jennifer L Stundon

Neuro Oncol. 2022 Dec 20:noac278. doi: 10.1093/neuonc/noac278. Online ahead of print.

ABSTRACT

BACKGROUND: To achieve replicative immortality, most cancers develop a telomere maintenance mechanism, such as reactivation of telomerase or alternative lengthening of telomeres (ALT). There are limited data on the prevalence and clinical significance of ALT in pediatric brain tumors, and ALT-directed therapy is not available.

METHODS: We performed C-circle analysis (CCA) on 579 pediatric brain tumors that had corresponding tumor/normal whole genome sequencing through the Open Pediatric Brain Tumor Atlas (OpenPBTA). We detected ALT in 6.9% (n=40/579) of these tumors and completed additional validation by ultrabright telomeric foci in situ on a subset of these tumors. We used CCA to validate TelomereHunter for computational prediction of ALT status and focus subsequent analyses on pediatric high-grade glioma (pHGG) Finally, we examined whether ALT is associated with recurrent somatic or germline alterations.

RESULTS: ALT is common in pHGG (n=24/63, 38.1%), but occurs infrequently in other pediatric brain tumors (<3%). Somatic ATRX mutations occur in 50% of ALT+ pHGG and in 30% of ALT- pHGG. Rare pathogenic germline variants in mismatch repair (MMR) genes are significantly associated with an increased occurrence of ALT.

CONCLUSIONS: We demonstrate that ATRX is mutated in only a subset of ALT+ pHGG, suggesting other mechanisms of ATRX loss of function or alterations in other genes may be associated with the development of ALT in these patients. We show that germline variants in MMR are associated with development of ALT in patients with pHGG.

PMID:36541551 | DOI:10.1093/neuonc/noac278

Permalink for 'Tissue and cell specific properties of enterochromaffin cells affect the fate of tumorigenesis toward non-endocrine adenocarcinoma of the small intestine'

Tissue and cell specific properties of enterochromaffin cells affect the fate of tumorigenesis toward non-endocrine adenocarcinoma of the small intestine

Fetched: December 21st, 2022, 5:01am GMT by Yoshitatsu Sei

Am J Physiol Gastrointest Liver Physiol. 2022 Dec 20. doi: 10.1152/ajpgi.00205.2022. Online ahead of print.

ABSTRACT

Small intestinal neuroendocrine tumor SI-NETs are serotonin-secreting well-differentiated neuroendocrine tumors of putative enterochromaffin (EC) cell origin. However, EC cell-derived tumorigenesis remains poorly understood. Here we examined whether the gain of Myc and the loss of RB1 and Trp53 function in EC cells result in SI-NET using tryptophan hydroxylase 1 (TPH1) Cre-ERT2-driven RB1^fl Trp53^fl Myc^LSL (RPM) mice. TPH1-Cre induced gain of Myc and loss of RB1 and Trp53 function resulted in endocrine or neuronal tumors in pancreas, lung, enteric neurons, and brain. Lineage tracing indicated that the cellular origin for these tumors was TPH1-expressing neuroendocrine, neuronal or their precursor cells in these organs. However, despite that TPH1 is most highly expressed in EC cells, we observed no incidence of EC cell tumors. Instead, the tumor of epithelial cell-origin in the intestine was exclusively non-endocrine adenocarcinoma, suggesting dedifferentiation of EC cells into intestinal stem cells (ISC). Further, ex-vivo organoid studies indicated that loss of functions of Rb1 and Trp53 accelerated dedifferentiation of EC cells that were susceptible to apoptosis with expression of activated MycT58A, suggesting that the rare dedifferentiating cells escaping cell death went on to develop adenocarcinomas. Lineage tracing demonstrated that EC cells were short-lived compared to neuroendocrine or neuronal cells in other organs. In contrast, EC cell-derived ISCs were long-lasting and actively cycling and thus susceptible to transformation. These results suggest that tissue- and cell-specific properties of EC cells affect the fate and rate of tumorigenesis induced by genetic alterations and provide important insights into EC cell-derived tumorigenesis.

PMID:36537709 | DOI:10.1152/ajpgi.00205.2022

Permalink for 'Treatment Outcome of Gamma-Knife Radiosurgery for Brain Metastasis from Thyroid Cancer: Favorable Local Control but Poor Survival'

Treatment Outcome of Gamma-Knife Radiosurgery for Brain Metastasis from Thyroid Cancer: Favorable Local Control but Poor Survival

Fetched: December 20th, 2022, 5:01am GMT by Joonho Byun

World Neurosurg. 2022 Dec 17:S1878-8750(22)01774-0. doi: 10.1016/j.wneu.2022.12.070. Online ahead of print.

ABSTRACT

BACKGROUND: Brain metastasis from thyroid cancer (TCBM) is extremely rare; thus, despite a good treatment outcome for thyroid cancer, TCBM has shown poor clinical outcomes. Considering the short survival and poor general condition of patients with TCBM, stereotactic radiosurgery may be preferred to achieve local control.

METHODS: A total of 25 patients with TCBM who underwent Gamma Knife radiosurgery (GKS) were initially included in this study; however, 3 patients were excluded because of a lack of data.

RESULTS: There were 7 men (31.8%) and 15 women (68.2%) and the mean age was 63.7 years. The most common type of thyroid cancer histology was papillary carcinoma. Fourteen patients (63.6%) harbored single brain metastatic tumor and 8 (36.3%) had multiple brain metastatic tumors. The mean duration from thyroid cancer diagnosis to detection of brain metastasis was 7.7 years (range, 0-23 years). The median dose of radiation of GKS was 22 Gy (range, 18-25 Gy). There was no radiation-induced complication after GKS. The median overall survival (OS) was 15 months and the 1-year OS of patients with TCBM was 63%, the 2-year OS was 38%, and the 5-year OS was 28%. The 6-month progression-free survival (PFS) for local recurrence of TCBM was 90.4%, the 1-year PFS was 84%, and the 3-year PFS was 84%.

CONCLUSIONS: GKS showed favorable local control for TCBM. However, the rate of distant brain metastasis was high and median survival of patients with TCBM was only 15 months.

PMID:36535554 | DOI:10.1016/j.wneu.2022.12.070

Permalink for 'Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis'

Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis

Fetched: December 20th, 2022, 5:01am GMT by Margarita Zaytseva

Neuro Oncol. 2022 Dec 19:noac274. doi: 10.1093/neuonc/noac274. Online ahead of print.

ABSTRACT

BACKGROUND: Choroid plexus carcinomas (CPCs) are rare aggressive pediatric tumors of the brain with no treatment standards. Genetic profiling of CPCs is often confined to possible association with Li-Fraumeni syndrome, though only about a half of CPCs develop from syndromic predispositions. Whole-chromosome gains and losses typical of CPCs reflect genomic instability of these tumors, but only partially explain the aggressive clinical course.

METHODS: This retrospective study enrolled 25 pediatric patients with CPC, receiving treatment between January 2009 and June 2022. Molecular genetic testing was performed for 20 cases with available tumor tissue and encompassed mutational status, chromosomal aberrations and gene expression profiles. We analyzed several factors presumably influencing the outcomes, including molecular profiles and clinical parameters. The median follow-up constituted 5.2 years (absolute range 2.8-12.6 years).

RESULTS: All studied CPCs had smooth mutational profiles with the only recurrent event being TP53 variants, either germline or somatic, encountered in 13 cases. Unbalanced whole-chromosome aberrations, notably multiple monosomies, were highly typical. In seven tumors, chromosome losses were combined with complex genomic rearrangements: segmental gains and losses or signs of chromothripsis. This phenomenon was associated with extremely low 5-year survival: 20.0±17.9% vs. 85.7±13.2%; p=0.009. Transcriptomically, the cohort split into two polar clusters Ped_CPC1 and Ped_CPC2 differing by survival: 31.3±17.8% vs. 100%; p=0.012.

CONCLUSION: CPCs split into at least two molecular subtypes distinguished both genomically and transcriptomically. Clusterization of the tumors into Ped_CPC1 and Ped_CPC2 significantly correlates with survival. The distinction may prove relevant in clinical trials for dedicated and patient-oriented optimization of clinical protocols for these rare tumors.

PMID:36534940 | DOI:10.1093/neuonc/noac274

The spectrum of morphological findings in pediatric central nervous system MN1-fusion-positive neuroepithelial tumors

Fetched: December 20th, 2022, 5:01am GMT by Fabiana Lubieniecki

Childs Nerv Syst. 2022 Dec 19. doi: 10.1007/s00381-022-05741-y. Online ahead of print.

ABSTRACT

PURPOSE: Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS-HGNET-MN1) is a rare entity defined by its DNA methylation pattern and pathologically considered to be high-grade with mixed patterns, stromal hyalinization, and with astrocytic differentiation. Our aim was to present six pediatric cases to contribute to the characterization of this group of tumors.

MATERIAL AND METHODS: Six female patients aged 4 to 12 years with CNS tumors with MN1 alteration identified using genome-wide methylation arrays and/or RT-PCR were included. Clinicopathological, morphological, immunohistochemical, and molecular findings were analyzed.

RESULTS: Tumor location was the parietal lobe in four and the intramedullary spinal cord in two. Two were morphologically diagnosed as ependymomas, one as gliofibroma, one as a HGNET-MN1 altered and the other two were difficult to classify. All were well-defined tumors, with a cystic component in three. Only two tumors had extensive stromal hyalinization, three had pseudopapillary formations, and four had other patterns. Multinucleated, clear, and rhabdoid cells were present. Necrosis and histiocyte clusters were also observed. Proliferative index was >10 in four. GFAP, EMA, CK, and SYN were variable, while Olig2 staining was mostly positive. Four of six patients with supratentorial tumors and complete resections were alive and tumor free after 2 to 10 years of follow-up. The two cases with medullary involvement and incomplete resections were alive and undergoing treatment 2 years after surgery.

CONCLUSION: Neuroepithelial-MN1 tumors are challenging and suspicion requires molecular confirmation. Our pediatric data contribute to the knowledge for accurate diagnosis. Although further studies with a larger number of cases should be conducted in order to draw more robust conclusions regarding clinico-pathological features, here we present valuable pediatric data to increase the knowledge that may lead to the accurate management of this group of tumors.

PMID:36534132 | DOI:10.1007/s00381-022-05741-y

A rare case of bladder cancer that metastasized to brain, heart, and lung lymph nodes benefited from immunotherapy

Fetched: December 19th, 2022, 5:01am GMT by Lian-Kai Zhu

World J Surg Oncol. 2022 Dec 19;20(1):402. doi: 10.1186/s12957-022-02876-9.

ABSTRACT

Bladder cancer is a common malignant tumor of the genitourinary system, with the primary cause of death being metastasis. The most common metastatic sites are the lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland, and the intestine. Brain and heart metastases are rare. In this report, we describe a patient who had pulmonary lymph node metastases more than a year after being diagnosed with bladder cancer, followed by brain and cardiac metastases more than two years later. Following the failure of standard first-line chemotherapy, the patient accepted 6 cycles of tislelizumab immunotherapy. The re-examination revealed that the bilateral frontal brain metastases had vanished, the right temporal lobe metastases had been greatly decreased, the neurological symptoms had been alleviated, and the cardiac metastases had disappeared. This is a rare clinical case with encouraging effects of tislelizumab and can serve as a model for the treatment of similar patients.

PMID:36529739 | PMC:PMC9762084 | DOI:10.1186/s12957-022-02876-9

Gastrointestinal Stromal Tumor With a Rare Associated Meningioma: A Case Report

Fetched: December 17th, 2022, 5:01am GMT by Daniel Miller

Cureus. 2022 Nov 11;14(11):e31361. doi: 10.7759/cureus.31361. eCollection 2022 Nov.

ABSTRACT

Gastrointestinal stromal tumors (GISTs) tend to be associated with other tumors. In certain familial cancer syndromes, GIST has been associated with breast cancer or other endocrine tumors. Multiple endocrine neoplasia syndrome along with certain other genomic mutations such as succinate dehydrogenase complex mutations described GIST as one of the potential tumors of the syndrome. There has not yet been a definite association between GIST and meningioma. We present a case of a patient with a GIST who was later found to have a meningioma on incidental brain imaging. Despite being a benign tumor not requiring additional intervention, it is quite apparent that providers need to have a low threshold to scan for other tumors if suspicious symptoms arise.

PMID:36523671 | PMC:PMC9744389 | DOI:10.7759/cureus.31361

Permalink for 'Combination of transsphenoidal endoscopic surgery and presurgical somatostatin analogs in thyrotropin (TSH)-secreting pituitary adenomas: Treatment outcome and long-term remission at a single pituitary center'

Combination of transsphenoidal endoscopic surgery and presurgical somatostatin analogs in thyrotropin (TSH)-secreting pituitary adenomas: Treatment outcome and long-term remission at a single pituitary center

Fetched: December 17th, 2022, 5:01am GMT by Jie Liu

Front Endocrinol (Lausanne). 2022 Nov 28;13:1061029. doi: 10.3389/fendo.2022.1061029. eCollection 2022.

ABSTRACT

BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) account for an extremely rare group of pituitary adenomas. Few studies examined the sensitivity and efficacy of presurgical somatostatin analogs (SSAs) and described the long-term remission under such treatment modality. The aim of the present study was to assess the efficacy of presurgical SSA treatment and long-term remission after surgery.

METHODS: A retrospective cohort of 65 TSHoma patients who received endoscopic transsphenoidal pituitary surgery between 2011 and 2020 in a single pituitary center in China was established. Data were analyzed for sex differences and different types of SSA and ultimately to explore the hormonal cutoff for remission prediction.

RESULTS: TSHomas had a predominant female preference in this cohort (43 women vs. 22 men). Baseline FT3 was higher in men [7.543 ± 2.407 vs. 5.58 (4.99, 6.58), p = 0.019], which was consistent with its longer diagnosis time and larger tumor volume. The median medication time for hormonal control was 2. 5 days for short-acting SSA and 4. 0 weeks for long-term SSA. Patients with long-acting SSA had a shrinking maximum tumor diameter at a median of 1.0 (-1.6, 4.925) mm. Only 10 patients (15.38%) were not in complete remission among whom 8 patients were not en-bloc resected and 2 patients had tumor recurrence after 81.6 and 10. 7 months of complete removal. Postsurgical thyroid hormones (within 1 week) of TSH <0.094 μIU/ml were identified as the cutoff for remission using the ROC curve.

CONCLUSIONS: The combination of endoscopic transsphenoidal surgery and presurgical SSA TSHomas provided a higher long-term remission for TSHomas.

PMID:36518240 | PMC:PMC9742421 | DOI:10.3389/fendo.2022.1061029

Permalink for 'Electrochemical biosensors in exosome analysis; a short journey to the present and future trends in early-stage evaluation of cancers'

Electrochemical biosensors in exosome analysis; a short journey to the present and future trends in early-stage evaluation of cancers

Fetched: December 16th, 2022, 5:01am GMT by Ehsan Dezhakam

Biosens Bioelectron. 2023 Feb 15;222:114980. doi: 10.1016/j.bios.2022.114980. Epub 2022 Dec 10.

ABSTRACT

The tumor microenvironment consists of a multiplicity of cells such as cancer cells, fibroblasts, endothelial cells, and immune cells within the specific parenchyma. It has been indicated that cancer cells can educate other cells within the tumor niche in a paracrine manner by the release of nano-sized extracellular vesicles namely exosomes (Exo), resulting in accelerated tumor mass growth. It is suggested that exosomal cargo with remarkable information can reflect any changes in metabolic and proteomic profiles in parent tumor cells. Therefore, exosomes can be touted as prognostic, diagnostic, and therapeutic elements with specific biomarkers in patients with different tumor types. Despite the advantages, conventional exosome separation and purification protocols are time-consuming and laborious with low abnormal morphology and purity rate. During the last decades, biosensor-based modalities, as emerging instruments, have been used to detect and analyze Exo in biofluids. Due to suitable specificity, sensitivity, and real-time readout, biosensors became promising approaches for the analysis of Exo in in vitro and in vivo settings. The inherent advantages and superiority of electrochemical biosensors in the determination of tumor grade based on exosomal cargo and profile were also debated. Present and future challenges were also discussed related to the application of electrochemical biosensors in the clinical setting. In this review, the early detection of several cancer types associated with ovaries, breast, brain, colon, lungs, T and B lymphocytes, liver and rare types of cancers were debated in association with released exosomes.

PMID:36521207 | DOI:10.1016/j.bios.2022.114980

Permalink for 'Knockdown of lncRNA SNHG16 Attenuates the Proliferation and Radioresistance of Nasopharyngeal Carcinoma Cells by Mediating miR-31-5p/SFN Axis'

Knockdown of lncRNA SNHG16 Attenuates the Proliferation and Radioresistance of Nasopharyngeal Carcinoma Cells by Mediating miR-31-5p/SFN Axis

Fetched: December 16th, 2022, 5:01am GMT by Weiwei Zhang

Radiat Res. 2022 Dec 15. doi: 10.1667/RADE-22-00163.1. Online ahead of print.

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a rare head and neck tumor that threatens people's health. Radiotherapy is a major treatment for NPC, however, radioresistance of the NPC cells may contribute to treatment failure. LncRNA SNHG16 was upregulated in NPC; however, the function of SNHG16 in radioresistant NPC cells remains unexplored. RT-qPCR was applied for detecting SNHG16, miR-31-5p and SFN levels. MTT assay and colony formation assay were applied to assess the cell viability and proliferation. Dual luciferase was applied for assessing the relation among SNHG16, miR-31-5p and SFN. SFN level in NPC cells was examined by Western blot. The level of SNHG16 and SFN in NPC cells was significantly upregulated by exposure to radiation. In addition, silencing of SNHG16 or miR-31-5p mimics notably attenuated radioresistance of NPC cells. SNHG16 could positively regulate the expression of SFN in NPC cells through binding with miR-31-5p. Furthermore, SNHG16 downregulation obviously attenuated the proliferation and radioresistance of NPC cells by regulation of miR-31-5p/SFN axis. Knockdown of lncRNA SNHG16 attenuates radioresistance of nasopharyngeal carcinoma cells by miR-31-5p/SFN axis. Thus, our research data show a novel method for improving the efficacy of radiotherapy for NPC.

PMID:36520963 | DOI:10.1667/RADE-22-00163.1

Permalink for 'Electrocorticography-Guided Resection Enhances Postoperative Seizure Freedom in Low-Grade Tumor-Associated Epilepsy: A Systematic Review and Meta-Analysis'

Electrocorticography-Guided Resection Enhances Postoperative Seizure Freedom in Low-Grade Tumor-Associated Epilepsy: A Systematic Review and Meta-Analysis

Fetched: December 16th, 2022, 5:01am GMT by Nebras M Warsi

Neurosurgery. 2023 Jan 1;92(1):18-26. doi: 10.1227/neu.0000000000002182. Epub 2022 Nov 3.

ABSTRACT

BACKGROUND: Low-grade cerebral neoplasms are commonly associated with medically intractable epilepsy. Despite increasing evidence that epileptogenic brain regions commonly extend beyond visible tumor margins, the utility of extended surgical resections leveraging intraoperative electrocorticography (ECoG) remains unclear.

OBJECTIVE: To determine whether ECoG-guided surgery is associated with improved postoperative seizure control.

METHODS: We performed a systematic review and meta-analysis encompassing both adult and pediatric populations. The primary outcome measure was postoperative seizure freedom as defined by Engel class I outcome. Class I/II outcome served as a secondary measure. Relevant clinical and operative data were recorded. A random-effects meta-analysis based on the pooled odds ratio (OR) of seizure freedom was performed on studies that reported comparative data between ECoG-guided surgery and lesionectomy.

RESULTS: A total of 31 studies encompassing 1115 patients with medically refractory epilepsy met inclusion criteria. Seven studies reported comparative data between ECoG-guided surgery and lesionectomy for meta-analysis. Tumor resection guided by ECoG was associated with significantly greater postoperative seizure freedom (OR 3.95, 95% CI 2.32-6.72, P < .0001) and class I/II outcome (OR 5.10, 95% CI 1.97-13.18, P = .0008) compared with lesionectomy. Postoperative adverse events were rare in both groups.

CONCLUSION: These findings provide support for the utilization of ECoG-guided surgery to improve postoperative seizure freedom in cases of refractory epilepsy associated with low-grade neoplasms. However, this effect may be attenuated in the presence of concomitant cortical dysplasia, highlighting a need for improved presurgical and intraoperative monitoring for these most challenging cases of localization-related epilepsy.

PMID:36519857 | DOI:10.1227/neu.0000000000002182

Endoscopic Management of Malignant Tumors of Paranasal Sinus and Nasal Cavity: An Institutional Experience

Fetched: December 16th, 2022, 5:01am GMT by Rajat Jain

Indian J Otolaryngol Head Neck Surg. 2022 Dec;74(4):564-574. doi: 10.1007/s12070-022-03141-x. Epub 2022 Sep 9.

ABSTRACT

Malignant tumors of sinonasal region are rare and affect less than 1 in 100,000 people per year. They are histologically diverse group and potentially pose significant management problems due to their proximity to the orbit and intracranial cavity. Although squamous cell carcinoma (SCC) is most common malignant tumor of paranasal cavity, tumors like adenocarcinoma, olfactory neuroblastoma, malignant melanoma, adenoid cystic carcinoma, sarcomas, haemoproliferative tumors, e.g. lymphoma may also occur. Retrospectively study was done in a tertiary care institute from January 2008 to December 2018 in India. Inclusion criteria-all biopsy proven PNS malignancy patients operated by endoscopic approach, irrespective of age and gender. Exclusion criteria- patients diagnosed with nasopharyngeal carcinoma, skin involvement, gross orbital involvement (muscle invasion), metastasis, operated by open approaches. 46 patients who underwent endoscopic tumor removal were reviewed. 36 (78.2%) were males and 10 (4.6%) females. Most common tumor in our study was adenoid cystic carcinoma. Recurrence was seen in 6 patients. Palliative therapy was given to all patients with recurrence. Management of malignant PNS tumor involving anterior skull base is multidisciplinary. R0 resection should be main goal in all malignant PNS malignancy. Tumors invading unresectable areas like cavernous sinus, brain parenchyma, carotids can be left in these places followed by palliation except in cases of squamous cell carcinoma. If R0 cannot be achieved surgically in SCC than patient should be considered inoperable and send for palliation. T1-T3 PNS malignant tumors can be managed by endoscopic approach followed by adjuvant therapy after a period of 6 weeks. Endoscopic excision should be converted to endoscopic assisted open approach in case of T4 tumors. We have tried to give a management protocol for management of malignant PNS tumors. Level of evidence: II.

PMID:36514438 | PMC:PMC9741682 | DOI:10.1007/s12070-022-03141-x

Debut of gastric cancer with brain metastasis: clinical surgical management

Fetched: December 16th, 2022, 5:01am GMT by Javier Romero

Rev Gastroenterol Peru. 2022 Apr-Jun;42(2):117-121.

ABSTRACT

Gastric cancer is one of the most frequent worldwide. Brain metastases from gastric cancer are rare and are diagnosed in less than 1% of patients with gastric cancer. We present the case of a 61-year-old woman with a history of decreased visual acuity, headache, and involuntary movements. She underwent an MRI that showed a left occipital extraparenchymal appearance lesion. The PET scan reveals a hypermetabolic zone in the lesser curvature of the stomach, and the endoscopy reveals a lesion suggestive of gastric malignant neoplasia in the Borrmann I fundus. It was decided to perform a tumor excision by neurosurgery, whose pathological anatomy study revealed metastatic adenocarcinoma to the brain. She undergoes a total D2 gastrectomy, no other metastases are evident. The patient evolves favorably in the postoperative period. The pathology study revealed a poorly differentiated adenocarcinoma. In Peru and in the world, standard recommendations on how to treat these patients have not yet been established, although it is known that surgical resection of brain metastases can significantly decrease morbidity and prolong survival compared to non-surgical approaches. As far as we know, it is the first report of this type presented in the country.

PMID:36513357

Cerebellar metastasis of colon cancer at diagnosis: A very rare case

Fetched: December 16th, 2022, 5:01am GMT by Melih Simsek

J Cancer Res Ther. 2022 Dec;18(Supplement):S493-S494. doi: 10.4103/jcrt.JCRT_514_20.

ABSTRACT

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Besides, brain metastasis from CRC is relatively rare. A 68-year-old male referred to the emergency clinic with headache, vertigo, nausea, and vomiting. A cerebellar mass lesion was determined and totally excised. Pathology revealed a metastatic adenocarcinoma. Colonoscopic biopsy obtained from the lesion in the colon was reported as adenocarcinoma. A cerebellar recurrent lesion occurred, and radiotherapy was initiated. After radiotherapy, FOLFOX-bevacizumab combination regimen was initiated as the first-line treatment of the patient with metastatic colon cancer. Significant improvements in the clinical outcomes of CRC were achieved in recent years. However, brain metastasis from CRC has a poor prognosis. We aimed to report a rare presentation of CRC with synchronous brain metastasis.

PMID:36511013 | DOI:10.4103/jcrt.JCRT_514_20

Rare Cancer News & Clinical Trials » PubMed - Rare Brain Tumor

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