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Hou P, Liu M, Li Z, Cai M, Cai C. Spinal cord metastasis in a long-term survivor of primary malignant glioblastoma: A case report. Oncol Lett 2025; 30:343. [PMID: 40438875 PMCID: PMC12117526 DOI: 10.3892/ol.2025.15089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 04/17/2025] [Indexed: 06/01/2025] Open
Abstract
Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Extracranial metastasis (ECM) is rare and usually indicates poor prognosis. We report a case of a 31-year-old female with GBM who underwent gross total resection followed by standard chemoradiotherapy. For recurrence, she received tumor treating fields and bevacizumab. At 23 months post-surgery, she developed COVID-19 pneumonia treated with dexamethasone, followed by spinal symptoms. MRI revealed L1-L2 lesions, and pathology after lumbar surgery confirmed ECM. Despite further treatment, the patient died of respiratory failure at 28 months. The present case illustrates the aggressive nature of ECM in GBM and the limited efficacy of current therapies in metastatic settings. Surgical resection and chemoradiotherapy remain the mainstay, while emerging treatments may provide hope for recurrent cases. Supportive care plays a critical role in advanced disease stages.
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Affiliation(s)
- Pengwei Hou
- Department of Neurosurgery, Shanghai Sixth People's Hospital Fujian, Jinjiang, Fujian 362200, P.R. China
| | - Meiyan Liu
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China
| | - Ziqi Li
- Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China
| | - Mingfa Cai
- Department of Neurosurgery, Shanghai Sixth People's Hospital Fujian, Jinjiang, Fujian 362200, P.R. China
| | - Chenzhu Cai
- Department of Neurosurgery, Shanghai Sixth People's Hospital Fujian, Jinjiang, Fujian 362200, P.R. China
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Rathi A, Choudhari AK, Chatterjee A, Sahay A, Bhattacharya K, Sahu A, Puranik AD, Shah A, Dasgupta A, Gupta T, Epari S. Spinal Diffuse Midline Glioma H3 K27M-Altered: Report of a Rare Tumor with Extracranial Skeletal Metastases and Review of Literature. Int J Surg Pathol 2025; 33:907-915. [PMID: 39376094 DOI: 10.1177/10668969241286243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Abstract
Diffuse midline glioma, H3 K27-altered is a rare and aggressive pediatric brain tumor with a grim prognosis. Diffuse midline glioma is characterized by specific molecular alterations, including H3 K27 mutations, and involves deep midline structures such as the brainstem, cerebellum, spinal cord, and thalamus. These tumors present with a classic triad of symptoms and have limited surgical options due to their challenging locations. Extra-neural metastases are an unusual occurrence in diffuse midline glioma and have been rarely described. Here we report a 17-year-old girl with spinal diffuse midline glioma, H3 K27M-mutant, who presented with multiple metastatic osseous lesions confirmed on biopsy of the thoracic vertebral lesion. Due to the rapid disease progression, the patient was recommended palliative therapy. Extra-neural metastases in diffuse midline glioma are rare, with only 16 reported patients, and no standard therapy exists. An accurate and early diagnosis is necessary to develop a personalized plan of treatment. Further research is needed to gain insights into the molecular pathology of diffuse midline glioma, H3 K27-altered, and improve the quality of life and the outcome of patients with this deadly disease.
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Affiliation(s)
- Aditi Rathi
- Department of Pathology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Amit Kumar Choudhari
- Department of Radiology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Abhishek Chatterjee
- Department of Nuclear Medicine, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Ayushi Sahay
- Department of Pathology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Kajari Bhattacharya
- Department of Radiology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Arpita Sahu
- Department of Radiology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Ameya D Puranik
- Department of Nuclear Medicine, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Aekta Shah
- Department of Pathology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Archya Dasgupta
- Department of Radiation Oncology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Tejpal Gupta
- Department of Radiation Oncology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Sridhar Epari
- Department of Pathology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
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3
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Jiang Z, Cai C, Shaikh N, Hyman W. Glioblastoma with metastasis to the bone marrow. BMJ Case Rep 2025; 18:e260883. [PMID: 40355275 DOI: 10.1136/bcr-2024-260883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025] Open
Abstract
Extraneural metastasis of glioblastoma (GBM) is rare but expected to increase in incidence as patients live longer. We present a rare case of GBM that has metastasised to the bone marrow shortly after completing standard of care treatment. This case highlights the importance of having a high index of suspicion, using next-generation sequencing testing and the urgent need for further research to identify treatment options for this population.
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Affiliation(s)
- Zhixin Jiang
- Hematology & Oncology, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Chunyu Cai
- Department of Pathology, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Nawal Shaikh
- UT Southwestern Medical Center, Dallas, Texas, USA
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4
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Pepper NB, Steike DR, Yppärilä-Wolters H, Müther M, Wiewrodt D, Berssenbrügge H, Grauer O, Lenz P, Stummer W, Eich HT. Multidisciplinary treatment is necessary in glioblastoma with extracerebral metastases. Strahlenther Onkol 2025; 201:420-430. [PMID: 39843784 PMCID: PMC11928418 DOI: 10.1007/s00066-024-02359-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 12/15/2024] [Indexed: 01/24/2025]
Abstract
PURPOSE While glioblastoma is the most common malignant brain tumor in adults, extracerebral manifestations are very rare in this highly aggressive disease with poor prognosis. METHODS We conducted a systematic literature review in the PubMed database and complemented the data by inclusion of a case treated in our clinic. In this context, we report on a 60-year-old woman with a right frontal glioblastoma, IDH wildtype, MGMT methylated. RESULTS Six months after initial diagnosis and primary treatment, there was extensive local intracranial progression with additional extension into the subcutaneous and frontotemporal cranial bones. Despite continuation of multimodal treatment, further extracerebral manifestations occurred 11 months after the initial diagnosis, both in the cranial bone as well as metastases in the right parotid gland, cervical lymph nodes, and lungs. While local radiotherapy enabled the cerebral lesions to be controlled, the patient's clinical condition deteriorated rapidly despite simultaneous systemic therapy. The treatment had to be discontinued, and the patient died 5 weeks after confirmation of the multilocal extracerebral manifestations and a total of 12 months after initial diagnosis. CONCLUSION Extracerebral manifestations of glioblastoma require close collaboration and joint decision-making with the patient, with an emphasis on palliative strategies.
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Affiliation(s)
- Niklas B Pepper
- Department of Radiation Oncology, University Hospital of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany.
| | - David R Steike
- Department of Radiation Oncology, University Hospital of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany
| | - Heidi Yppärilä-Wolters
- Department of Radiation Oncology, University Hospital of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany
| | - Michael Müther
- Department of Neurosurgery, University Hospital Muenster, Muenster, Germany
| | - Dorothee Wiewrodt
- Department of Neurosurgery, University Hospital Muenster, Muenster, Germany
| | - Hendrik Berssenbrügge
- Department of ear, nose and throat medicine, University Hospital Muenster, Muenster, Germany
| | - Oliver Grauer
- Department of Neurology with Institute of Translation Neurology, University Hospital Muenster, Muenster, Germany
| | - Philipp Lenz
- Department of Palliative Care, University Hospital Muenster, Muenster, Germany
| | - Walter Stummer
- Department of Neurosurgery, University Hospital Muenster, Muenster, Germany
| | - Hans T Eich
- Department of Radiation Oncology, University Hospital of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany
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5
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Basem JI, Seidman R, Franceschi D, Dashti R. Extraneural metastases of glioblastoma: A case report and literature review. Surg Neurol Int 2025; 16:102. [PMID: 40206754 PMCID: PMC11980742 DOI: 10.25259/sni_969_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 01/24/2025] [Indexed: 04/11/2025] Open
Abstract
Background Glioblastoma (isocitrate dehydrogenase [IDH]-wildtype, WHO Grade 4) is known to have a high recurrence rate with poor management of morbidity and mortality. Metastatic spread of glioblastomas is rare with extraneural osseous spread having been reported in under 100 cases. In this report, a case of glioblastoma with widespread extraneural metastatic lesions, including distal extremities, is presented. Case Description A 70-year-old female presented with progressive word-finding difficulty and confusion. Brain magnetic resonance imaging (MRI) revealed a 5 × 7 cm left temporal solid and cystic mass with heterogenous contrast enhancement and significant surrounding edema. She underwent near-total tumor resection, and the pathological diagnosis was glioblastoma, (IDH-wildtype, WHO grade 4), with sarcomatous and primitive neuronal components. She received radiation therapy and temozolomide over 4 months. At 5 months postoperative, she presented with new bilateral lower extremity weakness and left facial droop. MRI and positron emission tomography scans revealed local recurrence and metastatic lesions to vertebrae, extremities, and lymph nodes. Conclusion Previous research into rare glioblastoma bone metastases supports the theories of spread through hematogenous routes, surgical disruption, glymphatic system, and potential genetic susceptibility. However, no literature to date can adequately explain the distal limb metastases presented in this case, which shows the necessity for further understanding of this pathology.
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Affiliation(s)
- Jade I. Basem
- Department of Neurological Surgery, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
| | - Roberta Seidman
- Department of Pathology, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
| | - Dinko Franceschi
- Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
| | - Reza Dashti
- Department of Neurological Surgery, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
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6
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Eldaya RW, Kaya D, Williams M, Calle S, Schellingerhout D. Clinical and Imaging Features of Head and Neck Metastasis of High-Grade Glioma: A Single-Center Case Series. AJNR Am J Neuroradiol 2025; 46:160-165. [PMID: 39667825 PMCID: PMC11735445 DOI: 10.3174/ajnr.a8521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 06/28/2024] [Indexed: 12/14/2024]
Abstract
High-grade gliomas are the most frequent primary brain tumors, yet extraneural metastasis is exceedingly rare. This is in part secondary to the relatively poor survival of these patients and likely the shielding effect of the blood-brain barrier. Given the rarity of extraneural metastasis, the pathophysiology and imaging appearance of extraneural metastasis is under-reported and poorly understood. In this case series we present 6 patients with pathology-confirmed high-grade glioma and extraneural head and neck metastasis. We highlight imaging features of metastasis on CT, MRI, and PET/CT. We also explore potential correlations and pathophysiology of high-grade glioma metastasis to the head and neck region.
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Affiliation(s)
- Rami W Eldaya
- From the Department of Neuroradiology (R.W.E., D.K., S.C.), The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Diana Kaya
- From the Department of Neuroradiology (R.W.E., D.K., S.C.), The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michelle Williams
- Department of Anatomical Pathology (M.W.), The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Susana Calle
- From the Department of Neuroradiology (R.W.E., D.K., S.C.), The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Dawid Schellingerhout
- Departments of Neuroradiology and Imaging Physics (D.S.), The University of Texas MD Anderson Cancer Center, Houston, Texas
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7
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Laurin BJ, Treffy R, Connelly JM, Straza M, Mueller WM, Krucoff MO. Mesenchymal-Type Genetic Mutations Are Likely Prerequisite for Glioblastoma Multiforme to Metastasize Outside the Central Nervous System: An Original Case Series and Systematic Review of the Literature. World Neurosurg 2025; 193:397-426. [PMID: 39419169 DOI: 10.1016/j.wneu.2024.09.138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 09/30/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Glioblastoma multiforme (GBM) is the most aggressive and prevalent type of malignant brain tumor, yet it metastasizes outside the central nervous system (CNS) in only 0.4% of cases. Little is known about what enables this subset of GBMs to take root outside the CNS, but genetic mutations likely play a role. METHODS We conducted a PRISMA-compliant systematic review of metastatic GBM wherein we reviewed 3579 search results and 1080 abstracts, analyzing data from 139 studies and 211 unique patients. In addition, we describe 4 cases of patients with pathologically confirmed GBM metastases outside the CNS treated at our institution. RESULTS We found that metastases were discovered near previous surgical sites in at least 36.9% of cases. Other sites of metastasis included bone (47.9%), lung (25.6%), lymph nodes (25.1%), scalp (19.2%), and liver (14.2%). On average, metastases were diagnosed 12.1 months after the most recent resection, and the mean survival from discovery was 5.7 months. In our patients, primary GBM lesions showed mutations in NF1, TERT, TP53, CDK4, and RB1/PTEN genes. Unique to the metastatic lesions were amplifications in genes such as p53 and PDGFRA/KIT, as well as increased vimentin and Ki-67 expression. CONCLUSIONS There is strong evidence that GBMs acquire novel mutations to survive outside the CNS. In some cases, tumor cells likely mutate after seeding scalp tissue during surgery, and in others, they mutate and spread without surgery. Future studies and genetic profiling of primary and metastatic lesions may help uncover the mechanisms of spread.
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Affiliation(s)
- Bryce J Laurin
- School of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
| | - Randall Treffy
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Jennifer M Connelly
- Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Michael Straza
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Wade M Mueller
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Max O Krucoff
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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8
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Shen H, Mei Q, Chai X, Jiang Y, Liu A, Liu J. The prognostic significance of synchronous metastasis in glioblastoma multiforme patients: a propensity score-matched analysis using SEER data. Front Neurol 2024; 15:1429826. [PMID: 39440248 PMCID: PMC11493671 DOI: 10.3389/fneur.2024.1429826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
Background Glioblastoma multiforme (GBM) with synchronous metastasis(SM) is a rare occurrence. We extracted the data of GBM patients from the SEER database to look into the incidence of SM in GBM, determine the prognostic significance of SM in GBM, and assess therapeutic options for patients presenting with SM. Methods From 2004 to 2015, information on GBM patients was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching (PSM) method was employed to mitigate confounding factors between SM and non-SM groups, subsequently investigating the prognostic significance of SM in patients with GBM. Multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic variables for GBM patients with SM. A forest plot was used to visualize the results. Results A cohort of 19,708 patients was obtained from the database, among which 272 (1.4%) had SM at the time of diagnosis. Following PSM at a 3:1 ratio, in both univariate and multivariate cox regression analysis, SM (HR = 1.27, 95% CI: 1.09-1.46) was found to be an independent predictive predictor for GBM patients. Furthermore, the Cox proportional hazard forest plot demonstrated that independent risk variables for GBM patients with SM included age (Old vs. Young, HR = 1.44, 95% CI: 1.11-1.88), surgery (biopsy vs. no surgery, HR = 0.67, 95% CI: 0.46-0.96;Subtotal resection vs. no surgery, HR = 0.47, 95% CI: 0.32-0.68;Gross total resection vs. no surgery, HR = 0.44, 95% CI: 0.31-0.62), radiotherapy (HR = 0.58, 95% CI: 0.41-0.83), and chemotherapy (HR = 0.51, 95% CI: 0.36-0.72). Conclusion The predictive value of SM in GBM was determined by this propensity-matched analysis using data from the SEER database. Radiotherapy, chemotherapy, and surgery constitute an effective treatment regimen for patients with SM. A more positive approach toward the use of aggressive treatment for GBM patients with SM may be warranted.
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Affiliation(s)
- Hui Shen
- Department of Interventional Neuroradiology, Sanbo Brain Hospital, Capital Medical University, Beijing, China
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Qing Mei
- Department of Neurology, Beijing Pinggu Hospital, Beijing, China
| | - Xubin Chai
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Yuanfeng Jiang
- Department of Interventional Neuroradiology, Sanbo Brain Hospital, Capital Medical University, Beijing, China
| | - Aihua Liu
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Jiachun Liu
- Department of Interventional Neuroradiology, Sanbo Brain Hospital, Capital Medical University, Beijing, China
- Department of Neurosurgery, Beijing Hospital, Beijing, China
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9
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Heinig S, Aigner T, Bloß HG, Grabenbauer GG. Spinal and cervical nodal metastases in a patient with glioblastoma. Strahlenther Onkol 2024; 200:838-843. [PMID: 38488900 DOI: 10.1007/s00066-024-02214-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/04/2024] [Indexed: 03/17/2024]
Abstract
This article presents the rare case of a 54-year-old gentleman with primary glioblastoma developing multiple extracranial metastases 7 months after diagnosis. Initially, the patient complained of progressive headaches, confusion, and weakness of the left arm. Magnetic resonance imaging of the brain showed a right temporoparietal tumor with substantial surrounding subcortical edema and midline shift to the left. Two consecutive craniotomies resulted in complete microsurgical resection of the lesion. Histology was consistent with a World Health Organization grade IV, IDH-wildtype glioblastoma. Further treatment was standard chemoradiation including intensity-modulated radiotherapy with oral temozolomide chemotherapy. Seven months after diagnosis, the cranial lesion progressed, and the patient developed painful metastases in multiple bones and suspicious right-sided cervical lymph nodes. Immunohistochemistry and molecular signature supported the case of a metastatic glioblastoma. Further treatment was palliative radiotherapy of the spinal lesions along with symptomatic pain management. Extracranial metastasis of glioblastoma is a rare complication of which only a few cases have been reported in the literature. Little is known about the precise mechanisms of tumor dissemination and the appropriate treatment.
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Affiliation(s)
- Silvio Heinig
- Department of Radiation Oncology, Coburg Cancer Center, Coburg, Germany
- University of Split School of Medicine, Split, Croatia
| | - Thomas Aigner
- Department of Molecular Pathology, Coburg Cancer Center, Coburg, Germany
| | - Heinz-Georg Bloß
- Department of Neurosurgery, Coburg Cancer Center, Lichtenfels, Germany
| | - Gerhard G Grabenbauer
- Department of Radiation Oncology, Coburg Cancer Center, Coburg, Germany.
- University of Split School of Medicine, Split, Croatia.
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10
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Yuen CA, Pekmezci M, Bao S, Kong XT. Metastatic glioblastoma to the lungs: a case report and literature review. CNS Oncol 2024; 13:2351789. [PMID: 38864820 PMCID: PMC11172249 DOI: 10.1080/20450907.2024.2351789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 05/02/2024] [Indexed: 06/13/2024] Open
Abstract
Glioblastoma is the most common malignant primary brain tumor. Despite its infiltrative nature, extra-cranial glioblastoma metastases are rare. We present a case of a 63-year-old woman with metastatic glioblastoma in the lungs. Sarcomatous histology, a reported risk factor for disseminated disease, was found. Genomic alterations of TP53 mutation, TERT mutation, PTEN mutation, and +7/-10 were also uncovered. Early evidence suggests these molecular aberrations are common in metastatic glioblastoma. Treatment with third-line lenvatinib resulted in a mixed response. This case contributes to the growing body of evidence for the role of genomic alterations in predictive risk in metastatic glioblastoma. There remains an unmet need for treatment of metastatic glioblastoma.
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Affiliation(s)
- Carlen A Yuen
- Department of Neurology, Division of Neuro-Oncology, University of California, Irvine, CA92868, USA
| | - Melike Pekmezci
- Department of Pathology, University of California, San Francisco, CA94143, USA
| | - Silin Bao
- Department of Internal Medicine, Division of Neurosciences, Community Regional Medical Center, Fresno, CA93721, USA
| | - Xiao-Tang Kong
- Department of Neurology, Division of Neuro-Oncology, University of California, Irvine, CA92868, USA
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11
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Rolling CC, Mohme M, Bokemeyer C, Westphal M, Riethdorf S, Lamszus K, Pantel K, Klingler F, Langer F. Circulating Tumor Cells and Thromboembolic Events in Patients with Glioblastoma. Hamostaseologie 2024. [PMID: 38636546 DOI: 10.1055/a-2251-6766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2024] Open
Abstract
Patients with glioblastoma (GBM) are at increased risk for arterial and venous thromboembolism (TE). Risk factors include surgery, the use of corticosteroids, radiation, and chemotherapy, but also prothrombotic characteristics of the tumor itself such as expression of tissue factor, vascular endothelial growth factor, or podoplanin. Although distant metastases are extremely rare in this tumor entity, circulating tumor cells (CTCs) have been detected in a significant proportion of GBM patients, potentially linking local tumor growth characteristics to systemic hypercoagulability. We performed post hoc analysis of a study, in which GBM patients had been investigated for CTCs. Information on TE was retrieved from electronic patient charts. In total, 133 patients (median age, 63 years; interquartile range, 53-70 years) were analyzed. During follow-up, TE was documented in 14 patients (11%), including 8 venous and 6 arterial events. CTCs were detected in 26 patients (20%). Four (15%) patients with CTCs had a TE compared with 10 (9%) patients without CTCs. There was no difference in the frequency of TE events between patients with and those without detectable CTCs (p = 0.58). In summary, although our study confirms a high risk of TE in GBM patients, it does not point to an obvious association between CTCs and vascular thrombosis.
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Affiliation(s)
- Christina C Rolling
- Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Malte Mohme
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Carsten Bokemeyer
- Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Manfred Westphal
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sabine Riethdorf
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katrin Lamszus
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Klaus Pantel
- Department of Tumour Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Felix Klingler
- Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Florian Langer
- Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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12
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O'Neill K, Syed N, Crook T, Dubey S, Potharaju M, Limaye S, Ranade A, Anichini G, Patil D, Datta V, Datar R. Profiling of circulating glial cells for accurate blood-based diagnosis of glial malignancies. Int J Cancer 2024; 154:1298-1308. [PMID: 38146864 DOI: 10.1002/ijc.34827] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 11/17/2023] [Accepted: 11/29/2023] [Indexed: 12/27/2023]
Abstract
Here, we describe a blood test for the detection of glial malignancies (GLI-M) based on the identification of circulating glial cells (CGCs). The test is highly specific for GLI-M and can detect multiple grades (II-IV) and subtypes including gliomas, astrocytomas, oligodendrogliomas, oligoastrocytomas and glioblastomas, irrespective of gender and age. Analytical validation of the test was performed as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Real-world performance characteristics of the test were evaluated in four clinical (observational) studies. The test has high analytical sensitivity (95%), specificity (100%) and precision (coefficient of variation [CV] = 13.7% for repeatability and CV = 23.5% for within laboratory precision, both at the detection threshold) and is not prone to interference from common drugs and serum factors. The ability of the test to detect and differentiate GLI-M from non-malignant brain tumours (NBT), brain metastases from primary epithelial malignancies (EPI-M) and healthy individual donors (HD) was evaluated in four clinical cohorts. Across these clinical studies, the test showed 99.35% sensitivity (95% confidence interval [CI]: 96.44%-99.98%) and 100% specificity (95% CI: 99.37%-100%). The performance characteristics of this test support its clinical utility for diagnostic triaging of individuals presenting with intracranial space-occupying lesions (ICSOL).
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Affiliation(s)
- Kevin O'Neill
- Department of Neurosurgery, Imperial College Healthcare NHS Trust, London, UK
| | - Nelofer Syed
- Department of Brain Sciences, Hammersmith Hospital, Imperial College London, London, UK
| | - Timothy Crook
- Department of Brain Sciences, Hammersmith Hospital, Imperial College London, London, UK
| | - Sudhir Dubey
- Institute of Neurosciences, Medanta-The Medicity, Gurugram, India
| | - Mahadev Potharaju
- Department of Radiation Oncology, Apollo Speciality Hospitals, Chennai, India
| | - Sewanti Limaye
- Department of Medical and Precision Oncology, Sir HN Reliance Foundation Hospital and Research Centre, Mumbai, India
| | | | - Giulio Anichini
- Department of Brain Sciences, Hammersmith Hospital, Imperial College London, London, UK
| | - Darshana Patil
- Department of Research and Innovations, Datar Cancer Genetics, Nasik, India
| | - Vineet Datta
- Department of Research and Innovations, Datar Cancer Genetics, Nasik, India
| | - Rajan Datar
- Department of Research and Innovations, Datar Cancer Genetics, Nasik, India
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13
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Salvato I, Marchini A. Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives. Cancers (Basel) 2024; 16:1276. [PMID: 38610954 PMCID: PMC11010873 DOI: 10.3390/cancers16071276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 03/14/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
Despite decades of research and the best up-to-date treatments, grade 4 Glioblastoma (GBM) remains uniformly fatal with a patient median overall survival of less than 2 years. Recent advances in immunotherapy have reignited interest in utilizing immunological approaches to fight cancer. However, current immunotherapies have so far not met the anticipated expectations, achieving modest results in their journey from bench to bedside for the treatment of GBM. Understanding the intrinsic features of GBM is of crucial importance for the development of effective antitumoral strategies to improve patient life expectancy and conditions. In this review, we provide a comprehensive overview of the distinctive characteristics of GBM that significantly influence current conventional therapies and immune-based approaches. Moreover, we present an overview of the immunotherapeutic strategies currently undergoing clinical evaluation for GBM treatment, with a specific emphasis on those advancing to phase 3 clinical studies. These encompass immune checkpoint inhibitors, adoptive T cell therapies, vaccination strategies (i.e., RNA-, DNA-, and peptide-based vaccines), and virus-based approaches. Finally, we explore novel innovative strategies and future prospects in the field of immunotherapy for GBM.
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Affiliation(s)
- Ilaria Salvato
- NORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health (LIH), L-1210 Luxembourg, Luxembourg;
- Laboratory of Oncolytic Virus Immuno-Therapeutics (LOVIT), Department of Cancer Research, Luxembourg Institute of Health (LIH), L-1210 Luxembourg, Luxembourg
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine (FSTM), University of Luxembourg, L-4367 Belvaux, Luxembourg
| | - Antonio Marchini
- Laboratory of Oncolytic Virus Immuno-Therapeutics (LOVIT), Department of Cancer Research, Luxembourg Institute of Health (LIH), L-1210 Luxembourg, Luxembourg
- Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, 69120 Heidelberg, Germany
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14
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Ge X, Yang Y, Wang W, Tian L, Zhang G, Tian Z, Xue X. Pediatric H3K27M‑mutant diffuse midline glioma with vertebral metastasis: A case report and literature review. Oncol Lett 2024; 27:48. [PMID: 38192660 PMCID: PMC10773191 DOI: 10.3892/ol.2023.14181] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 11/07/2023] [Indexed: 01/10/2024] Open
Abstract
H3K27M-mutant diffuse midline glioma (DMG) is a type of high-grade glial tumor, which occurs in the midline structure and develops mostly in children. Extraneural metastases (ENM) are exceedingly rare in patients with H3K27M-mutant DMG. A 9-year-old male patient presented with a headache, nausea and vomiting. Following magnetic resonance imaging and immunohistochemical molecular testing examination, the patient was diagnosed with H3K27M-mutant DMG and received chemoradiotherapy plus five cycles of chemotherapy with temozolomide intermittently as an adjuvant therapy. The treatment resulted in a slight reduction of the tumor volume. However, 2 months later, the patient was admitted to hospital with complaints of drooping of the mouth, and waist and back pain. Magnetic resonance imaging and positron-emission tomography-computed tomography revealed an unusual presentation with multiple vertebral metastases and craniospinal leptomeningeal dissemination. Following discussion between the members of a multidisciplinary medical team, the patient underwent one cycle of chemotherapy with cyclophosphamide, vincristine and cisplatin. However, the condition did not improve and the patient died 4 weeks after the diagnosis of ENM. The mechanisms underlying the development of these rare metastases remain unclear. The present case report provides insights into the clinical characteristics and potential metastasis mechanisms of this aggressive disease and may help to elucidate new pathways for the management of ENM.
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Affiliation(s)
- Xiaohui Ge
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Yu Yang
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Wenyan Wang
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Lei Tian
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Ge Zhang
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Zhesen Tian
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Xiaoying Xue
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
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15
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Kurdi M, Baeesa S, Okal F, Bamaga AK, Faizo E, Fathaddin AA, Alkhotani A, Karami MM, Bahakeem B. Extracranial metastasis of brain glioblastoma outside CNS: Pathogenesis revisited. Cancer Rep (Hoboken) 2023; 6:e1905. [PMID: 37814403 PMCID: PMC10728524 DOI: 10.1002/cnr2.1905] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/16/2023] [Accepted: 09/19/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND The most prevalent malignant tumor of the CNS in adults is glioblastoma. Despite undergoing surgery and chemoradiotherapy, the prognosis remains unfavorable, with a median survival period ranging between 15 and 20 months. The incidence of glioblastoma metastasis outside CNS is uncommon with only 0.4%-2% reported rate, compared to other tumors that exhibit a 10% incidence rate of metastasis to the brain. On average, it takes about 11 months from the time of initial diagnosis for the tumor to spread beyond CNS. Consequently, the prognosis for metastatic glioblastoma is grim, with a 6-month survival rate following diagnosis. FINDINGS The rarity of extracranial metastasis is attributed to the blood-brain barrier and lack of a lymphatic drainage system, although rare cases of hematogenous spread and direct implantation have been reported. The possible mechanisms remain unclear and require further investigation. Risk factors have been widely described, including previous craniotomy or biopsies, ventricular shunting, young age, radiation therapy, prolonged survival time, and tumor recurrence. Due to the lack of understanding about extracranial metastasis of glioblastoma pathogenesis, no effective treatment exists to date. Aggressive chemotherapies are not recommended for metastatic glioblastoma as their side effects may worsen the patient prognosis. CONCLUSION The optimal treatment for extracranial metastasis of glioblastoma requires further investigation with a wide inclusion of patients. This review discusses the possible causes, factors, and underlying mechanisms of glioblastoma metastasis to different organs.
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Affiliation(s)
- Maher Kurdi
- Department of Pathology, Faculty of MedicineKing Abdulaziz UniversityRabighSaudi Arabia
| | - Saleh Baeesa
- Department of NeurosciencesKing Faisal Specialist Hospital and Research CenterJeddahSaudi Arabia
| | - Fahad Okal
- Department of Neuroscience, Neurosurgery Section, King Abdulaziz Medical CityNational Guard Health AffairsJeddahSaudi Arabia
| | - Ahmed K. Bamaga
- Department of Paediatric, Faculty of MedicineKing Abdulaziz University and HospitalJeddahSaudi Arabia
| | - Eyad Faizo
- Department of Surgery, Faculty of MedicineUniversity of TabukTabukSaudi Arabia
| | - Amany A. Fathaddin
- Department of Pathology, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
| | - Alaa Alkhotani
- Department of Pathology, College of MedicineUmm Al‐Qura UniversityMeccaSaudi Arabia
| | - Mohammed M. Karami
- Department of Clinical Physiology, Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
| | - Basem Bahakeem
- Department of Internal MedicineUmm‐Alqura UniversityMeccaSaudi Arabia
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16
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Kanemitsu T, Furuse M, Kuwabara H, Yagi R, Hiramatsu R, Kameda M, Nonoguchi N, Kawabata S, Takami T, Arai M, Wanibuchi M. Increasing C-reactive protein levels in a patient with glioblastoma with lymph node metastasis: a case report. BMC Neurol 2023; 23:354. [PMID: 37794336 PMCID: PMC10548662 DOI: 10.1186/s12883-023-03402-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 09/26/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND Glioblastoma usually recurs locally and extracranial metastases are rare. Most patients with extracranial metastases experience recurrence of the primary intracranial tumor. Lymph node metastases are often detected based on lymphadenopathy or symptoms caused by other metastatic sites. CASE PRESENTATION Herein, we report a case of glioblastoma with lymph node metastasis in which the patient was asymptomatic but exhibited gradually increasing C-reactive protein levels prior to becoming febrile 9 months after the initial C-reactive protein increase. Diagnosis of lymph node metastasis that was delayed because the patient had a fever of unknown origin, no signs of infection, and the primary intracranial tumor did not recur. Chest computed tomography indicated supraclavicular, mediastinal, and hilar lymphadenopathy, and biopsy identified lymph node metastasis of glioblastoma. This is the fifth reported case of lymph node metastasis without intracranial recurrence. CONCLUSIONS C-reactive protein levels may be a diagnostic marker for lymph node metastasis in patients with glioblastoma. Further evaluation is needed to elucidate the role of CRP in glioblastoma with lymph node metastasis.
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Affiliation(s)
- Takuya Kanemitsu
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
- Department of Neurosurgery, Midorigaoka Hospital, Takatsuki, Osaka, Japan
| | - Motomasa Furuse
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan.
| | - Hiroko Kuwabara
- Department of Pathology, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Ryokichi Yagi
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Ryo Hiramatsu
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Masahiro Kameda
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Naosuke Nonoguchi
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Shinji Kawabata
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Toshihiro Takami
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Motohiro Arai
- Department of Neurosurgery, Midorigaoka Hospital, Takatsuki, Osaka, Japan
| | - Masahiko Wanibuchi
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
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17
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Waack AL, Bhavsar AD, Ranabothu MR, Hoyt AT, Schroeder JL. Letter to the editor regarding "unusual extraneural metastasis of glioblastoma". Surg Neurol Int 2023; 14:302. [PMID: 37680923 PMCID: PMC10481798 DOI: 10.25259/sni_580_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 08/15/2023] [Indexed: 09/09/2023] Open
Affiliation(s)
- Andrew Leland Waack
- Department of Surgery, Division of Neurosurgery, University of Toledo, Toledo, Ohio, United States
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18
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Kamaleshwaran KK, Ramkumar E, Raghunathan MS. Whole-body 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Demonstrating Multiple Rare Extracranial Metastases in a Treated Case of Glioblastoma. Indian J Nucl Med 2023; 38:294-296. [PMID: 38046964 PMCID: PMC10693363 DOI: 10.4103/ijnm.ijnm_167_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 12/26/2022] [Accepted: 12/27/2022] [Indexed: 12/05/2023] Open
Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults that accounts for nearly 20% of all primary malignant brain tumors. While GBM is notable for local recurrence and invasion, extracranial metastases (ECMs) are exceedingly rare, occurring in <2% of patients. However, the report of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging in evaluating ECM is limited, and the importance of whole-body FDG PET/CT imaging in GBM has not been well elucidated. We present here a case of GBM, post excision 12 years before, whole-body 18F-FDG PET/CT showing no recurrence in the brain and ECM to multiple bones, right kidney, and pancreas.
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Affiliation(s)
| | - Elumalai Ramkumar
- Department of Nuclear Medicine, PET/CT and Radionuclide Therapy, Coimbatore, Tamil Nadu, India
| | - Madhu Sairam Raghunathan
- Department of Radiotherapy, Kovai Medical Center and Hospital Limited, Coimbatore, Tamil Nadu, India
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19
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Lessi F, Morelli M, Franceschi S, Aretini P, Menicagli M, Marranci A, Pasqualetti F, Gambacciani C, Pieri F, Grimod G, Zucchi V, Cupini S, Di Stefano AL, Santonocito OS, Mazzanti CM. Innovative Approach to Isolate and Characterize Glioblastoma Circulating Tumor Cells and Correlation with Tumor Mutational Status. Int J Mol Sci 2023; 24:10147. [PMID: 37373295 DOI: 10.3390/ijms241210147] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/08/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Circulating tumor cells (CTCs) are one of the most important causes of tumor recurrence and distant metastases. Glioblastoma (GBM) has been considered restricted to the brain for many years. Nevertheless, in the past years, several pieces of evidence indicate that hematogenous dissemination is a reality, and this is also in the caseof GBM. Our aim was to optimize CTCs' detection in GBM and define the genetic background of single CTCs compared to the primary GBM tumor and its recurrence to demonstrate that CTCs are indeed derived from the parental tumor. We collected blood samples from a recurrent IDH wt GBM patient. We genotyped the parental recurrent tumor tissue and the respective primary GBM tissue. CTCs were analyzed using the DEPArray system. CTCs Copy Number Alterations (CNAs) and sequencing analyses were performed to compare CTCs' genetic background with the same patient's primary and recurrent GBM tissues. We identified 210 common mutations in the primary and recurrent tumors. Among these, three somatic high-frequency mutations (in PRKCB, TBX1, and COG5 genes) were selected to investigate their presence in CTCs. Almost all sorted CTCs (9/13) had at least one of the mutations tested. The presence of TERT promoter mutations was also investigated and C228T variation was found in parental tumors and CTCs (C228T heterozygous and homozygous, respectively). We were able to isolate and genotype CTCs from a patient with GBM. We found common mutations but also exclusive molecular characteristics.
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Affiliation(s)
- Francesca Lessi
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Mariangela Morelli
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Sara Franceschi
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Paolo Aretini
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Michele Menicagli
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Andrea Marranci
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Francesco Pasqualetti
- Department of Radiation Oncology, Azienda Ospedaliera Universitaria Pisana, University of Pisa, 56122 Pisa, Italy
| | - Carlo Gambacciani
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Francesco Pieri
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Gianluca Grimod
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Vanna Zucchi
- Division of Pathology, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Samanta Cupini
- Division of Oncology, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Anna Luisa Di Stefano
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
- Neurology Department, Foch Hospital, 92150 Suresnes, France
| | - Orazio Santo Santonocito
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Chiara Maria Mazzanti
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
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20
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Akeret K, Weller M, Krayenbühl N. The anatomy of neuroepithelial tumours. Brain 2023:7171408. [PMID: 37201913 PMCID: PMC10393414 DOI: 10.1093/brain/awad138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 04/10/2023] [Accepted: 04/12/2023] [Indexed: 05/20/2023] Open
Abstract
Many neurological conditions conceal specific anatomical patterns. Their study contributes to the understanding of disease biology and to tailored diagnostics and therapy. Neuroepithelial tumours exhibit distinct anatomical phenotypes and spatiotemporal dynamics that differ from those of other brain tumours. Brain metastases display a preference for the cortico-subcortical boundaries of watershed areas and have a predominantly spherical growth. Primary CNS lymphomas localize to the white matter and generally invade along fibre tracts. In neuroepithelial tumours, topographic probability mapping and unsupervised topological clustering have identified an inherent radial anatomy and adherence to ventriculopial configurations of specific hierarchical orders. Spatiotemporal probability and multivariate survival analyses have identified a temporal and prognostic sequence underlying the anatomical phenotypes of neuroepithelial tumours. Gradual neuroepithelial de-differentiation and declining prognosis follow (i) an expansion into higher order radial units; (ii) a subventricular spread; and (iii) the presence of mesenchymal patterns (expansion along white matter tracts, leptomeningeal or perivascular invasion, CSF spread). While different pathophysiological hypotheses have been proposed, the cellular and molecular mechanisms dictating this anatomical behaviour remain largely unknown. Here we adopt an ontogenetic approach towards the understanding of neuroepithelial tumour anatomy. Contemporary perception of histo- and morphogenetic processes during neurodevelopment permit us to conceptualize the architecture of the brain into hierarchically organized radial units. The anatomical phenotypes in neuroepithelial tumours and their temporal and prognostic sequences share remarkable similarities with the ontogenetic organization of the brain and the anatomical specifications that occur during neurodevelopment. This macroscopic coherence is reinforced by cellular and molecular observations that the initiation of various neuroepithelial tumours, their intratumoural hierarchy and tumour progression are associated with the aberrant reactivation of surprisingly normal ontogenetic programs. Generalizable topological phenotypes could provide the basis for an anatomical refinement of the current classification of neuroepithelial tumours. In addition, we have proposed a staging system for adult-type diffuse gliomas that is based on the prognostically critical steps along the sequence of anatomical tumour progression. Considering the parallels in anatomical behaviour between different neuroepithelial tumours, analogous staging systems may be implemented for other neuroepithelial tumour types and subtypes. Both the anatomical stage of a neuroepithelial tumour and the spatial configuration of its hosting radial unit harbour the potential to stratify treatment decisions at diagnosis and during follow-up. More data on specific neuroepithelial tumour types and subtypes are needed to increase the anatomical granularity in their classification and to determine the clinical impact of stage-adapted and anatomically tailored therapy and surveillance.
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Affiliation(s)
- Kevin Akeret
- Department of Neurosurgery, Clinical Neuroscience Centre, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland
| | - Michael Weller
- Department of Neurology, Clinical Neuroscience Centre, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland
| | - Niklaus Krayenbühl
- Division of Paediatric Neurosurgery, University Children's Hospital, 8032 Zurich, Switzerland
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21
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Aymeric A, Louis-Marie T, Gabrielle C, Vincent J, Benoit M, Romuald S, Evelyne E, Luc B, Vincent R, Jimmy V, Christophe J, Emmanuel M, Leslie L, Bertrand M, Pierre-Jean LR, Andres C, Antoine P, Valérie R, Karima M, Audrey R, Philippe M, Dominique FB, Guillaume G, Kaissar F, Johan P, Ilyess Z. Natural history of spinal cord metastasis from brain glioblastomas. J Neurooncol 2023; 162:373-382. [PMID: 36991306 DOI: 10.1007/s11060-023-04298-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/13/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND AND OBJECTIVES Spinal cord metastasis arising from an intracranial glioblastoma is a rare and late event during the natural course of the disease. These pathological entities remain poorly characterized. This study aimed to identify and investigate the timeline, clinical and imaging findings, and prognostic factors of spinal cord metastasis from a glioblastoma. METHODS Consecutive histopathological cases of spinal cord metastasis from glioblastomas in adults entered in the French nationwide database between January 2004 and 2016 were screened. RESULTS Overall, 14 adult patients with a brain glioblastoma (median age 55.2 years) and harboring a spinal cord metastasis were included. The median overall survival as 16.0 months (range, 9.8-22.2). The median spinal cord Metastasis Free Survival (time interval between the glioblastoma diagnosis and the spinal cord metastasis diagnosis) was 13.6 months (range, 0.0-27.9). The occurrence of a spinal cord metastasis diagnosis greatly impacted neurological status: 57.2% of patients were not ambulatory, which contributed to dramatically decreased Karnofsky Performance Status (KPS) scores (12/14, 85.7% with a KPS score ≤ 70). The median overall survival following spinal cord metastasis was 3.3 months (range, 1.3-5.3). Patients with a cerebral ventricle effraction during the initial brain surgery had a shorter spinal cord Metastasis Free Survival (6.6 vs 18.3 months, p = 0.023). Out of the 14 patients, eleven (78.6%) had a brain IDH-wildtype glioblastoma. CONCLUSIONS Spinal cord metastasis from a brain IDH-wildtype glioblastoma has a poor prognosis. Spinal MRI can be proposed during the follow-up of glioblastoma patients especially those who have benefited from cerebral surgical resection with opening of the cerebral ventricles.
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Affiliation(s)
- Amelot Aymeric
- Department of Neurosurgery, CHRU de Tours, Tours, France.
- Service de Neurochirurgie, CHRU Bretonneau, 2 Boulevard Tonnellé, Tours Cedex 9, 37044, Tours, France.
| | - Terrier Louis-Marie
- Department of Neurosurgery, Clairval Private Hospital, Ramsay Generale de Sante, Marseille, France
| | - Cognacq Gabrielle
- University of Oxford, John Radcliffe HospitalHeadley Way, Headington, Oxford, OX3 9DU, Oxfordshire, United Kingdom
| | - Jecko Vincent
- Department of Neurosurgery A, CHU Pellegrin, Bordeaux, France
| | | | - Seizeur Romuald
- Department of Neurosurgery, CHU de La Cavale Blanche, Brest, France
| | - Emery Evelyne
- Department of Neurosurgery, CHU de Caen, Caen, France
| | - Bauchet Luc
- Department of Neurosurgery, Hôpital Saint Eloi - Gui de Chauliac, Montpellier, France
| | | | - Voirin Jimmy
- Department of Neurosurgery, Pasteur Hospital, HCC, Colmar, France
| | | | | | - Lemnos Leslie
- Department of Neurosurgery, CHU Dupuytren, Limoges, France
| | - Mathon Bertrand
- Department of Neurosurgery, CHU Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
| | | | - Coca Andres
- Department of Neurosurgery, CHU Strasbourg, Strasbourg, France
| | - Petit Antoine
- Department of Neurosurgery, CHU Jean-Minjoz, Besançon, France
| | - Rigau Valérie
- Department of Neuropathology, CHU Gui de Chauliac, Montpellier, France
| | - Mokhtari Karima
- Department of Neuropathology, Pitié-Salpêtrière, AP-HP, Paris, France
| | | | - Metellus Philippe
- Department of Neurosurgery, Clairval Private Hospital, Ramsay Generale de Sante, Marseille, France
| | | | | | - Farah Kaissar
- Department of Neurosurgery, CHU La Timone, Marseille, France
| | - Pallud Johan
- Department of Neurosurgery, GHU-Paris Psychiatrie Et Neurosciences, Hôpital Sainte-Anne, Paris, France
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22
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Aftahy AK, Butenschoen VM, Hoenikl L, Liesche-Starnecker F, Wiestler B, Schmidt-Graf F, Meyer B, Gempt J. A rare case of H3K27-altered diffuse midline glioma with multiple osseous and spinal metastases at the time of diagnosis. BMC Neurol 2023; 23:87. [PMID: 36855102 PMCID: PMC9972747 DOI: 10.1186/s12883-023-03135-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 02/21/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND H3K27-altered diffuse midline gliomas are uncommon central nervous system tumors with extremely poor prognoses. CASE PRESENTATION We report the case of a 24-year-old man patient with multiple, inter alia osseous metastases who presented with back pain, hemi-hypoesthesia, and hemi-hyperhidrosis. The patient underwent combined radio-chemotherapy and demonstrated temporary improvement before deteriorating. CONCLUSIONS H3K27-altered diffuse midline glioma presents an infrequent but crucial differential diagnosis and should be considered in cases with rapid neurological deterioration and multiple intracranial and intramedullary tumor lesions in children and young adults. Combined radio-chemotherapy delayed the neurological deterioration, but unfortunately, progression occurred three months after the diagnosis.
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Affiliation(s)
- A. Kaywan Aftahy
- grid.6936.a0000000123222966Department of Neurosurgery, School of Medicine, Medical Faculty, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
| | - Vicki M. Butenschoen
- grid.6936.a0000000123222966Department of Neurosurgery, School of Medicine, Medical Faculty, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
| | - Lisa Hoenikl
- grid.6936.a0000000123222966Department of Neurosurgery, School of Medicine, Medical Faculty, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
| | - Friederike Liesche-Starnecker
- grid.6936.a0000000123222966Department of Neuropathology, School of Medicine, Institute of Pathology, Technical University of Munich, Munich, Germany
| | - Benedikt Wiestler
- grid.6936.a0000000123222966Department of Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany
| | - Friederike Schmidt-Graf
- grid.6936.a0000000123222966Neurological Department, School of Medicine, Technical University of Munich, Munich, Germany
| | - Bernhard Meyer
- grid.6936.a0000000123222966Department of Neurosurgery, School of Medicine, Medical Faculty, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
| | - Jens Gempt
- grid.6936.a0000000123222966Department of Neurosurgery, School of Medicine, Medical Faculty, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
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Yang JF, Chen TM, Chang HH, Tsai YL, Tsai WC, Huang WY, Lo CH, Lin CS, Shen PC, Chen Y. Guggulsterone inhibits migration and invasion through proteasomal and lysosomal degradation in human glioblastoma cells. Eur J Pharmacol 2023; 938:175411. [PMID: 36436590 DOI: 10.1016/j.ejphar.2022.175411] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/28/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022]
Abstract
Glioblastoma multiforme (GBM) is a deadly brain malignancy, and current therapies offer limited survival benefit. The phytosterol guggulsterone (GS) has been shown to exhibit antitumor efficacy. This study aimed to investigate the effects of GS on migration and invasion and its underlying mechanisms in human GBM cell lines. After GS treatment, the survival rate of GBM cells was reduced, and the migration and invasion abilities of GBM cells were significantly decreased. There was also concomitant decreased expression of focal adhesion complex, matrix metalloproteinase-2 (MMP2), MMP9 and cathepsin B. Furthermore, GS induced ERK phosphorylation and autophagy, with increased p62 and LC3B-II expression. Notably, treatment of in GBM cells with the proteasome inhibitor MG132 or the lysosome inhibitor NH4Cl reversed the GS-mediated inhibition of migration and invasion. In an orthotopic xenograft mouse model, immunohistochemical staining of brain tumor tissues demonstrated that MMP2 and cathepsin B expression was reduced in GS-treated mice. GS treatment inhibited GBM cell migration and invasion via proteasomal and lysosomal degradation, suggesting its therapeutic potential in clinical use in the future.
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Affiliation(s)
- Jen-Fu Yang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzu-Min Chen
- Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
| | - Hsin-Han Chang
- Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Ling Tsai
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Chiuan Tsai
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Cheng-Hsiang Lo
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chun-Shu Lin
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan
| | - Po-Chien Shen
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ying Chen
- Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
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Matsuhashi A, Tanaka S, Takami H, Nomura M, Ikemura M, Matsubayashi Y, Shinoda Y, Yamada K, Sakai Y, Karasawa Y, Takayanagi S, Saito N. Recurrent glioblastoma metastatic to the lumbar vertebra: A case report and literature review: Surgical oncology. Front Oncol 2023; 13:1101552. [PMID: 36874120 PMCID: PMC9978767 DOI: 10.3389/fonc.2023.1101552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 01/31/2023] [Indexed: 02/18/2023] Open
Abstract
Background Glioblastoma is a malignant tumor, and its prognosis is as poor as 1.5 to 2 years. Most cases recur within one year even under the standard treatment. The majority of recurrences are local, and in rare cases, metastasize mostly within the centra nervous system. Extradural metastasis of glioma is exceedingly rare. Here, we present a case of vertebral metastasis of glioblastoma. Case presentation We present a 21-year-old man post total resection of the right parietal glioblastoma, diagnosed with lumbar metastasis. He originally presented with impaired consciousness and left hemiplegia and underwent gross total resection of the tumor. Given the diagnosis of glioblastoma, he was treated with radiotherapy combined with concurrent and adjuvant temozolomide. Six months after tumor resection, the patient presented with severe back pain, and was diagnosed as metastatic glioblastoma on the first lumbar vertebrae. Posterior decompression with fixation and postoperative radiotherapy were conducted. He went on to receive temozolomide and bevacizumab. However, at 3 months after the diagnosis of lumbar metastasis, further disease progression was noted, and his care was transitioned to best supportive care. Comparison on copy number status between primary and metastatic lesions on methylation array analysis revealed more enhanced chromosomal instability including 7p loss, 7q gain and 8 gain in the metastatic lesion. Conclusion Based upon the literature review and our case, younger age of initial presentation, multiple surgical interventions, and long overall survival seem to be the risk factors of vertebral metastasis. As the prognosis of glioblastoma improves over time, its vertebral metastasis is seemingly more common. Therefore, extradural metastasis should be kept in mind in the treatment of glioblastoma. Further, detailed genomic analysis on multiple paired specimens is mandated to elucidate the molecular mechanisms of vertebral metastasis.
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Affiliation(s)
- Ako Matsuhashi
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shota Tanaka
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Hirokazu Takami
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Masashi Nomura
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Masako Ikemura
- Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan
| | | | - Yusuke Shinoda
- Department of Rehabilitation Medicine, Saitama Medical University Hospital, Saitama, Japan
| | - Keisuke Yamada
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Yu Sakai
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Yasuaki Karasawa
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
| | | | - Nobuhito Saito
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
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25
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Kim YJ, Ahn KH, Lee KH, Moon KS. Case report: Fulminant extraneural metastasis of glioblastoma through venous sinus. Front Oncol 2022; 12:1034944. [PMID: 36338688 PMCID: PMC9633940 DOI: 10.3389/fonc.2022.1034944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/10/2022] [Indexed: 11/29/2022] Open
Abstract
Background Extraneural metastasis (ENM) of glioblastoma are rare. However, as patient overall survival improves, the incidence of ENM has gradually increased. Although several risk factors have been proposed, venous sinus invasion was regarded as a very exceptional route for ENM. Case description We report a 60-year-old man with glioblastoma in the temporal lobe, invading the transverse and sigmoid venous sinus. After gross total tumor resection, the patient received the standard chemoradiation therapy. Systemic evaluation for persistent shoulder and back pain revealed widespread metastasis to lymph nodes and multiple bones 9 months after surgery. Despite spine radiation therapy, the patient became paraplegic and died 1 year after surgery. Conclusions Venous sinus invasion should be kept in mind by physicians, as a risk factor for glioblastoma ENM. Systemic evaluation of these patients with extracranial symptoms should be performed without hesitation.
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Affiliation(s)
- Yeong Jin Kim
- Department of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanam-do, South Korea
| | - Kang Hee Ahn
- Department of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanam-do, South Korea
| | - Kyung-Hwa Lee
- Department of Pathology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanam-do, South Korea
- *Correspondence: Kyung-Sub Moon, ; Kyung-Hwa Lee,
| | - Kyung-Sub Moon
- Department of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanam-do, South Korea
- *Correspondence: Kyung-Sub Moon, ; Kyung-Hwa Lee,
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26
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Labak CM, Rabah NM, Kipke JP, Mahajan UV, Labak KB, Ali SA, Fowler N, Sloan AE. Multidisciplinary approaches to gliosarcoma: A case report and review of the literature. Clin Case Rep 2022; 10:e5985. [PMID: 36017117 PMCID: PMC9396286 DOI: 10.1002/ccr3.5985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 11/30/2022] Open
Abstract
A 58-year-old right-handed man presented to our tertiary care center with gliosarcoma (GS) infiltration through the dura, skull, and soft tissue. Patient had a previous history of right temporal GS, with four intracranial surgeries prior to presentation. A multidisciplinary approach was used to treat the lesion and perform reconstruction.
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Affiliation(s)
- Collin M. Labak
- Department of NeurosurgeryUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandOhioUSA
| | - Nicholas M. Rabah
- Department of NeurosurgeryUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandOhioUSA
| | - Jasmine P. Kipke
- Department of NeurosurgeryUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandOhioUSA
| | - Uma V. Mahajan
- Case Western Reserve University School of MedicineClevelandOhioUSA
| | | | - S. Ahmed Ali
- Department of OtolaryngologyUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandOhioUSA
| | - Nicole Fowler
- Department of OtolaryngologyUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandOhioUSA
- Seidman Cancer Center and Case Comprehensive Cancer CenterClevelandOhioUSA
| | - Andrew E. Sloan
- Department of NeurosurgeryUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandOhioUSA
- Seidman Cancer Center and Case Comprehensive Cancer CenterClevelandOhioUSA
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A Rare Case of Metastatic Glioblastoma Diagnosed by Endobronchial Ultrasound-Transbronchial Needle Aspiration. Case Rep Pulmonol 2022; 2022:5453420. [PMID: 35761950 PMCID: PMC9233607 DOI: 10.1155/2022/5453420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 05/15/2022] [Accepted: 06/03/2022] [Indexed: 12/16/2022] Open
Abstract
Glioblastoma is a common primary brain tumor that has a high mortality rate. Reports of intrathoracic metastases are uncommon, with the most commonly reported site for metastases are the lung and pleura. However, involvement of the mediastinum is not well documented, and few reports of confirmed mediastinal metastases diagnosed by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) exist. Herein, we report a rare case of metastatic glioblastoma to the thorax. A lady in her 40s has been previously diagnosed with intracranial glioblastoma with multiple incidences of disease recurrence despite treatment with chemoradiotherapy, adjuvant chemotherapy, and repeated surgical resections. She presented with dyspnea and pleural effusion, for which radiological imaging revealed lung, pleural, and mediastinal lesions. Further diagnostic workup with EBUS and pleural fluid sampling confirmed metastatic disease to both sites. The pleural fluid showed highly atypical cells positive for GFAP, and EBUS-TBNA immunostains were GFAP, S100, and synaptophysin positive, giving an overall picture consistent with metastatic glioblastoma. The patient was referred for palliative care, and unfortunately, she passed away after several months.
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28
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Dialogue among Lymphocytes and Microglia in Glioblastoma Microenvironment. Cancers (Basel) 2022; 14:cancers14112632. [PMID: 35681612 PMCID: PMC9179556 DOI: 10.3390/cancers14112632] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 02/06/2023] Open
Abstract
Simple Summary In this review, we summarize in vitro and in vivo studies related to glioblastoma models and human patients to outline the symbiotic bidirectional interaction between microglia, lymphocytes, and tumor cells that develops during tumor progression. Particularly, we highlight the current experimental therapeutic approaches that aim to shape these interplays, such as adeno-associated virus (AAV) delivery and CAR-T and -NK cell infusion, and to modulate the tumor microenvironment in an anti-tumoral way, thus counteracting glioblastoma growth. Abstract Microglia and lymphocytes are fundamental constituents of the glioblastoma microenvironment. In this review, we summarize the current state-of-the-art knowledge of the microglial role played in promoting the development and aggressive hallmarks of this deadly brain tumor. Particularly, we report in vitro and in vivo studies related to glioblastoma models and human patients to outline the symbiotic bidirectional interaction between microglia, lymphocytes, and tumor cells that develops during tumor progression. Furthermore, we highlight the current experimental therapeutic approaches that aim to shape these interplays, such as adeno-associated virus (AAV) delivery and CAR-T and -NK cell infusion, and to modulate the tumor microenvironment in an anti-tumoral way, thus counteracting glioblastoma growth.
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29
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Bone metastasis from glioblastoma: a systematic review. J Neurooncol 2022; 158:379-392. [PMID: 35578056 DOI: 10.1007/s11060-022-04025-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 04/27/2022] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Glioblastoma (GBM) is a devastating disease with poor overall survival. Despite the common occurrence of GBM among primary brain tumors, metastatic disease is rare. Our goal was to perform a systematic literature review on GBM with osseous metastases and understand the rate of metastasis to the vertebral column as compared to the remainder of the skeleton, and how this histology would fit into our current paradigm of treatment for bone metastases. METHODS A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was performed using the PubMed database from 1952 to 2021. Search terms included "GBM", "glioblastoma", "high-grade glioma", "bone metastasis", and "bone metastases". RESULTS Of 659 studies initially identified, 67 articles were included in the current review. From these 67 articles, a total of 92 distinct patient case presentations of metastatic glioblastoma to bone were identified. Of these cases, 58 (63%) involved the vertebral column while the remainder involved lesions within the skull, sternum, rib cage, and appendicular skeleton. CONCLUSION Metastatic dissemination of GBM to bone occurs. While the true incidence is unknown, workup for metastatic disease, especially involving the spinal column, is warranted in symptomatic patients. Lastly, management of patients with GBM vertebral column metastases can follow the International Spine Oncology Consortium two-step multidisciplinary algorithm for the management of spinal metastases.
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30
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Gharahkhani R, Pourhadi M, Mirdamadi NS, Dana N, Rafiee L, Nedaeinia R, Javanmard SH. Effect of Anti-Podoplanin on Malignant Glioma Cell Viability, Invasion and Tumor Cell-Induced Platelet Aggregation. Arch Med Res 2022; 53:461-468. [DOI: 10.1016/j.arcmed.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 02/05/2022] [Accepted: 05/06/2022] [Indexed: 11/02/2022]
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31
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Extraneural Metastases of Diffuse Midline Glioma, H3 K27M-Mutant at Diagnosis: Case Report, Review of the Literature, and Identifying Targetable Alterations. J Pediatr Hematol Oncol 2022; 44:e597-e604. [PMID: 33974582 DOI: 10.1097/mph.0000000000002189] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/25/2021] [Indexed: 11/26/2022]
Abstract
Extraneural metastases are rare in pediatric high-grade gliomas and little is known about the genomic profiles of tumors that disseminate beyond the central nervous system. We describe a pediatric patient with H3 K27M-mutant diffuse midline glioma of the brain and spine with biopsy-confirmed osseous metastases present at diagnosis and suspected metastatic parenchymal pulmonary disease. Several potentially clinically and/or therapeutically relevant genomic alterations were identified, including H3F3A and TP53 mutations as well as MET, CDK6, EMSY, and PIK3CG amplifications. Sequencing is critical to improve our understanding of the molecular drivers of distant metastases and discover therapeutic targets that penetrate all disease sites.
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32
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Jayarama-Naidu R, Gallus E. Abnormal Schwannoma-like Growth of multiple, multifocal BRAF V600E-positive Glioblastoma in the Interior Acoustic Canal with Leptomeningeal Infiltration: a case report. J Med Case Rep 2022; 16:50. [PMID: 35130969 PMCID: PMC8822757 DOI: 10.1186/s13256-022-03272-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 01/13/2022] [Indexed: 02/07/2023] Open
Abstract
Background Glioblastoma belongs to the most common and most aggressive tumor entity of the central nervous system with a poor prognosis of only few months. Once manifested, it grows fast and diffusely by infiltrating the surrounding brain parenchyma. Despite its aggressive behavior, glioblastoma rarely presents with multiple lesions and metastasis to intra- and extracranial tissues. Therefore, metastasized, multiple glioblastoma is limited to case reports. Our case describes an atypical primary bilateral manifestation of BRAF V600E-positive epithelioid glioblastoma with rapid metastasis and meningeosis glioblastoma while under adjuvant chemoradiotherapy. Case presentation A 60-year-old Caucasian male patient presented with a seizure and numbness in his left arm. He was diagnosed with an abnormal primary bilateral manifestation of multiple, multifocal BRAF V600E-positive and isocitrate dehydrogenase (IDH) wild-type intracranial epithelioid glioblastoma with O6-methylguanine-DNA methyltransferase methylation (MGMT) at 12%. While being under the adjuvant chemoradiotherapy with temozolomide, the patient developed left-sided facial nerve weakness and hearing loss, dysarthria, and severe gait instability. Cranial magnetic resonance imaging showed that glioblastoma lesions advanced rapidly with a schwannoma-like growth pattern by invading the left internal acoustic meatus, adjacent cranial nerves, and leptomeninges. A lumbar puncture confirmed meningeosis glioblastoma. Four months after the initial diagnosis of glioblastoma, the patient died from the complications of the fast and diffuse metastasis. Conclusions Glioblastoma rarely presents with metastases despite its aggressive and rapidly growing nature. Our case should increase awareness of symptom tracking in patients with glioblastoma to intervene early and efficiently. Moreover, refractory therapies for glioblastoma should underline the importance of personalized medicine.
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Affiliation(s)
- Roopa Jayarama-Naidu
- Department Internal Medicine, Kantonsspital Frauenfeld, Spital Thurgau AG, 8501, Frauenfeld, Switzerland.
| | - Evelyn Gallus
- Department Radiology, Kantonsspital Frauenfeld, Spital Thurgau AG, 8501, Frauenfeld, Switzerland
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33
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Yau DT, Lacambra MD, Chow C, To K. The Novel finding of an
FGFR1‐TACC1
Fusion in an Undifferentiated Spindle Cell Sarcoma of Soft Tissue with Aggressive Clinical Course. Genes Chromosomes Cancer 2022; 61:206-211. [PMID: 35064610 DOI: 10.1002/gcc.23024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 01/02/2022] [Accepted: 01/03/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Derek Tsz‐Wai Yau
- Department of Anatomical and Cellular Pathology the Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong SAR China
| | - Maribel D. Lacambra
- Department of Anatomical and Cellular Pathology the Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong SAR China
| | - Chit Chow
- Department of Anatomical and Cellular Pathology the Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong SAR China
| | - Ka‐Fai To
- Department of Anatomical and Cellular Pathology the Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong SAR China
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34
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Zhang W, Cai YY, Wang XL, Wang XX, Li Y, Han GY, Chu YJ, Zhang YX, Hao FR. Bone Metastases of Glioblastoma: A Case Report and Review of the Literature. Front Oncol 2021; 11:705455. [PMID: 34646764 PMCID: PMC8504694 DOI: 10.3389/fonc.2021.705455] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 09/02/2021] [Indexed: 01/05/2023] Open
Abstract
Background Glioblastoma (GBM) is the most common primary intracranial tumor and originates from the small pool of adult neural stem and progenitor cells (NSPCs). According to the World Health Organization (WHO) classification of brain tumors, gliomas are classified into grades I–IV, and GBM is defined as the highest grade (IV). GBM can be disseminated by cerebrospinal fluid (CSF), but extracranial metastasis is rare. Additionally, the pathway and mechanism involved remain unclear. Case Presentation We report a rare case of left temporal lobe GBM with multiple bone metastases and soft tissue metastasis. This 49-year-old right-handed man who was diagnosed with GBM underwent surgery on May 9, 2017, followed by radiochemotherapy in June 2017. On August 13, 2019, local relapse was found. Then, the patient received a second surgery but not radiochemotherapy. In November 2019, the patient was reported to be suffering from low back pain for nearly 1 month. On December 6, 2019, magnetic resonance imaging (MRI) of the thoracolumbar vertebrae and abdominal computed tomography (CT) confirmed metastases on the ninth posterior rib on the right, the third anterior rib on the left, and the T7 and T10 vertebrae and their appendages. CT-guided rib space-occupying puncture biopsy was performed, and GBM was identified by pathology. Conclusion We should pay attention to extracranial metastasis of GBM. Timely detection and early treatment improve overall quality of patients’ life. The extracranial metastasis in this patient may have occurred through the spinal nerve root or intercostal nerve. Further clinical observations are required to clarify the pathway and mechanism involved.
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Affiliation(s)
- Wei Zhang
- Clinical School, Weifang Medical University, Weifang, China
| | - Yuan-Yuan Cai
- Department of Radiation Oncology, Weifang People's Hospital, Weifang, China
| | - Xiao-Li Wang
- Department of Radiation Oncology, Weifang People's Hospital, Weifang, China
| | - Xiao-Xiao Wang
- Department of Radiation Oncology, Weifang People's Hospital, Weifang, China
| | - Yang Li
- Department of Radiation Oncology, Weifang People's Hospital, Weifang, China
| | - Gui-Yan Han
- Department of Pathology, Weifang People's Hospital, Weifang, China
| | - Yu-Jing Chu
- Department of Imaging, Weifang People's Hospital, Weifang, China
| | - Yun-Xiang Zhang
- Department of Pathology, Weifang People's Hospital, Weifang, China
| | - Fu-Rong Hao
- Department of Radiation Oncology, Weifang People's Hospital, Weifang, China.,Weifang Key Laboratory of Radiophysics and Oncological Radiobiology, Weifang, China
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35
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A subcutaneous mass due to a glioblastoma which invaded and destroyed the bone: A case report. INTERDISCIPLINARY NEUROSURGERY 2021. [DOI: 10.1016/j.inat.2021.101194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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36
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Schwock J, Mirham L, Ghorab Z. Cytology of Extraneural Metastases of Nonhematolymphoid Primary Central Nervous System Tumors: Six Cases with Histopathological Correlation and Literature Update. Acta Cytol 2021; 65:529-540. [PMID: 34311461 PMCID: PMC8686714 DOI: 10.1159/000517480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 05/27/2021] [Indexed: 01/30/2023]
Abstract
INTRODUCTION Extraneural/-cranial metastases (ENM) of primary central nervous system (CNS) tumors are rare and may be diagnostically challenging. We describe the cytomorphological and pertinent clinical features of ENM in a case series assessed by fine-needle aspiration (FNA). A search of the laboratory information systems of 2 tertiary care centers in Toronto (2000-2015) was performed. Cases with direct extracranial/-spinal extension of CNS neoplasms were excluded. Microscopic slides of FNA and surgical specimens were reviewed. Demographic and clinicopathological data were retrieved. CASE PRESENTATION Six cases were identified with the original diagnoses of glioblastoma, glioblastoma with primitive neuroectodermal tumor-like components, anaplastic ependymoma, myxopapillary ependymoma, atypical meningioma, and hemangiopericytoma. Median patient age at first diagnosis was 44 years (range 22-56). The time interval between initial diagnosis and first metastatic disease manifestation was 3 months to 19 years. All FNA diagnoses were rendered correctly. In 4 cases, immunohistochemistry was used to support the diagnosis. All cases had prior surgical intervention at the primary tumor site. In 4 cases, the ENM location was the ipsilateral parotid or buccal area. Two primary tumors in midline location developed ENM in the scapular area. DISCUSSION/CONCLUSION ENM are a rare manifestation of a range of different primary CNS tumors and may involve the ipsilateral head and neck mimicking clinically a salivary gland neoplasm. FNA can rapidly discriminate ENM from other, potentially more indolent conditions. Awareness of the clinical history is paramount to avoid diagnostic confusion.
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Affiliation(s)
- Joerg Schwock
- Division of Pathology, University Health Network, Toronto, Ontario, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Lorna Mirham
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Department of Laboratory Medicine, North York General Hospital, Toronto, Ontario, Canada
| | - Zeina Ghorab
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Division of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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So JS, Kim H, Han KS. Mechanisms of Invasion in Glioblastoma: Extracellular Matrix, Ca 2+ Signaling, and Glutamate. Front Cell Neurosci 2021; 15:663092. [PMID: 34149360 PMCID: PMC8206529 DOI: 10.3389/fncel.2021.663092] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/29/2021] [Indexed: 12/12/2022] Open
Abstract
Glioblastoma (GBM) is the most common and malignant form of primary brain tumor with a median survival time of 14–16 months in GBM patients. Surgical treatment with chemotherapy and radiotherapy may help increase survival by removing GBM from the brain. However, complete surgical resection to eliminate GBM is almost impossible due to its high invasiveness. When GBM cells migrate to the brain, they interact with various cells, including astrocytes, neurons, endothelial cells, and the extracellular matrix (ECM). They can also make their cell body shrink to infiltrate into narrow spaces in the brain; thereby, they can invade regions of the brain and escape from surgery. Brain tumor cells create an appropriate microenvironment for migration and invasion by modifying and degrading the ECM. During those processes, the Ca2+ signaling pathway and other signaling cascades mediated by various ion channels contribute mainly to gene expression, motility, and invasion of GBM cells. Furthermore, GBM cells release glutamate, affecting migration via activation of ionotropic glutamate receptors in an autocrine manner. This review focuses on the cellular mechanisms of glioblastoma invasion and motility related to ECM, Ca2+ signaling, and glutamate. Finally, we discuss possible therapeutic interventions to inhibit invasion by GBM cells.
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Affiliation(s)
- Jae-Seon So
- Department of Medical Biotechnology, Dongguk University-Gyeongju, Gyeongju, South Korea
| | - Hyeono Kim
- Department of Medical Biotechnology, Dongguk University-Gyeongju, Gyeongju, South Korea
| | - Kyung-Seok Han
- Department of Medical Biotechnology, Dongguk University-Gyeongju, Gyeongju, South Korea
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Ryzhova MV, Galstyan SA, Starovoitov DV, Snigireva GP, Zubova IV, Golanov AV, Pronin IN, Pavlova GV, Mertsalova MP, Belov AI, Kalinin PL, Serova NK. [Intraosseous metastasis of K27-mutant glioma]. Arkh Patol 2021; 83:40-44. [PMID: 34041895 DOI: 10.17116/patol20218303140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Glioma metastasis outside the central nervous system is a quite rare phenomenon. The disease in a young woman manifested itself as back pain and loss of vision in the left eye. Magnetic resonance imaging (MRI) revealed a tumor of the optic nerve; positron emission tomography showed multiple secondary bone changes. At the same time, MRI detected no signs of neoplasm in the midline brain structures (the brain stem and subcortical nuclei) and spinal cord. Two biopsies (superior iliac spine trephine biopsy and optic nerve tumor biopsy) were performed. There were similar histological tumors; the optic nerve tumor was found to have K27M mutation in the H3F3A gene, whereas the metastatic tumor lacked this mutation (possibly due to the quality and quantity of DNA isolated from the tumor cells). The interesting features of this case are the simultaneous detection of primary and metastatic tumors before receiving any treatment and the absence of the K27M mutation in the H3F3A gene in the metastasis.
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Affiliation(s)
- M V Ryzhova
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - S A Galstyan
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - D V Starovoitov
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - G P Snigireva
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - I V Zubova
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - A V Golanov
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - I N Pronin
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - G V Pavlova
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - M P Mertsalova
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - A I Belov
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - P L Kalinin
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
| | - N K Serova
- Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
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Mohiuddin S, Maraka S, Usman Baig M, Gupta S, Muzzafar T, Valyi-Nagy T, Lindsay H, Moody K, Razvi S, Paulino A, Slavin K, Gondi V, McCutcheon I, Zaky W, Khatua S. Case series of diffuse extraneural metastasis in H3F3A mutant high-grade gliomas: Clinical, molecular phenotype and literature review. J Clin Neurosci 2021; 89:405-411. [PMID: 34053821 DOI: 10.1016/j.jocn.2021.05.033] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 05/16/2021] [Accepted: 05/17/2021] [Indexed: 11/19/2022]
Abstract
H3K27M and H3.3G34R/V mutations have been identified in pediatric high-grade gliomas (pHGG), though extraneural metastases are rarely reported and poorly characterized. Three pHGG patients from two institutions were identified with extraneural metastasis, harboring histone mutations. Their clinical, imaging and molecular characteristics are reported here. A 17-year old female presented with supratentorial H3.3G34R-mutant glioma with metastatic osseous lesions in the spine, pelvis, bone marrow, pleural effusion and soft tissue of pelvis. Bone marrow biopsy and soft tissue of pelvis biopsy showed neoplastic cells positive for P53. A 20-year old female was diagnosed with H3F3A H3K27M-mutant thalamic glioma. She developed diffuse sclerotic osseous lesions. Biopsy of an osseous lesion was non-diagnostic. A 17-year old female presented with a H3F3A H3K27M-mutant diffuse midline glioma with diffuse spinal cord metastasis. She further developed multifocal chest lymphadenopathy, pleural effusions, and a soft tissue mass in the abdominal wall. The latter was positive for H3K27M mutation. We present the first case series of pHGG with H3F3A mutation and diffuse extraneural dissemination, describing their clinical and molecular profile.
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Affiliation(s)
- Sana Mohiuddin
- Department of Pediatrics Patient Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Stefania Maraka
- Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL, USA; Department of Neuro-oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Muhammad Usman Baig
- Department of Pediatrics Patient Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sumit Gupta
- Department of Pediatrics Patient Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tariq Muzzafar
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tibor Valyi-Nagy
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Holly Lindsay
- Department of Pediatrics, Division of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Karen Moody
- Department of Pediatrics Patient Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shehla Razvi
- Department of Pediatrics Patient Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Arnold Paulino
- Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Konstantin Slavin
- Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Vinai Gondi
- Northwestern Medicine Chicago Proton Center, Warrenville, IL, USA
| | - Ian McCutcheon
- Department of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Wafik Zaky
- Department of Pediatrics Patient Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Soumen Khatua
- Department of Hematology-Oncology, Mayo Clinic, Rochester, MN.
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Bunda S, Zuccato JA, Voisin MR, Wang JZ, Nassiri F, Patil V, Mansouri S, Zadeh G. Liquid Biomarkers for Improved Diagnosis and Classification of CNS Tumors. Int J Mol Sci 2021; 22:4548. [PMID: 33925295 PMCID: PMC8123653 DOI: 10.3390/ijms22094548] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/15/2021] [Accepted: 04/22/2021] [Indexed: 12/22/2022] Open
Abstract
Liquid biopsy, as a non-invasive technique for cancer diagnosis, has emerged as a major step forward in conquering tumors. Current practice in diagnosis of central nervous system (CNS) tumors involves invasive acquisition of tumor biopsy upon detection of tumor on neuroimaging. Liquid biopsy enables non-invasive, rapid, precise and, in particular, real-time cancer detection, prognosis and treatment monitoring, especially for CNS tumors. This approach can also uncover the heterogeneity of these tumors and will likely replace tissue biopsy in the future. Key components of liquid biopsy mainly include circulating tumor cells (CTC), circulating tumor nucleic acids (ctDNA, miRNA) and exosomes and samples can be obtained from the cerebrospinal fluid, plasma and serum of patients with CNS malignancies. This review covers current progress in application of liquid biopsies for diagnosis and monitoring of CNS malignancies.
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Affiliation(s)
- Severa Bunda
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
| | - Jeffrey A. Zuccato
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada
| | - Mathew R. Voisin
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada
| | - Justin Z. Wang
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada
| | - Farshad Nassiri
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada
| | - Vikas Patil
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
| | - Sheila Mansouri
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
| | - Gelareh Zadeh
- MacFeeters-Hamilton Center for Neuro-Oncology Research, 4-305 Princess Margaret Cancer Research Tower, 101 College Street, Toronto, ON M5G 1L7, Canada; (S.B.); (J.A.Z.); (M.R.V.); (J.Z.W.); (F.N.); (V.P.); (S.M.)
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada
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Liu J, Shen L, Tang G, Tang S, Kuang W, Li H, Tian Y, Zhou Q. Multiple extracranial metastases from glioblastoma multiforme: a case report and literature review. J Int Med Res 2021; 48:300060520930459. [PMID: 32552287 PMCID: PMC7303784 DOI: 10.1177/0300060520930459] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Extracranial metastasis from glioblastoma multiforme (GBM) is rare, especially
multi-site metastases without intracranial recurrence. However, the metastatic
mechanism of GBM remains unknown and there is currently no consensus regarding
the best therapeutic regimen. We report the case of a 46-year-old man with
primary GBM who developed scalp metastases and subsequent multiple pulmonary
metastases. He was treated with the Stupp regimen after surgery for the
intracranial tumor. However, a series of soft masses in the scalp were
subsequently identified, and new nodules were found in his left eyebrow arch
during chemoradiotherapy. Despite salvage chemotherapy and targeted therapy, the
patient eventually died of respiratory failure with multiple pulmonary
metastases. This case highlights the need for rigorous follow-up, including
brain magnetic resonance imaging, in patients with GBM. The occurrence of
extra-central nervous system symptoms indicates the possibility of metastasis,
and the relevant examinations should be conducted promptly. Positive therapies
may help to relieve symptoms and prolong survival in patients with metastatic
GBM.
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Affiliation(s)
- Jing Liu
- Department of Oncology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Guyu Tang
- Department of Urology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Siyuan Tang
- Department of Oncology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Weilu Kuang
- Department of Oncology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Huan Li
- Department of Oncology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Yifu Tian
- Department of Pathology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
| | - Qin Zhou
- Department of Oncology, Xiangya Hospital, Central South
University, Changsha, Hunan Province, People’s Republic of China
- Qin Zhou, Department of Oncology, Xiangya
Hospital, Central South University, No. 87, Xiangya Road, Kaifu District,
Changsha, Hunan Province 410008, China.
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Stanković T, Ranđelović T, Dragoj M, Stojković Burić S, Fernández L, Ochoa I, Pérez-García VM, Pešić M. In vitro biomimetic models for glioblastoma-a promising tool for drug response studies. Drug Resist Updat 2021; 55:100753. [PMID: 33667959 DOI: 10.1016/j.drup.2021.100753] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 02/16/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023]
Abstract
The poor response of glioblastoma to current treatment protocols is a consequence of its intrinsic drug resistance. Resistance to chemotherapy is primarily associated with considerable cellular heterogeneity, and plasticity of glioblastoma cells, alterations in gene expression, presence of specific tumor microenvironment conditions and blood-brain barrier. In an attempt to successfully overcome chemoresistance and better understand the biological behavior of glioblastoma, numerous tri-dimensional (3D) biomimetic models were developed in the past decade. These novel advanced models are able to better recapitulate the spatial organization of glioblastoma in a real time, therefore providing more realistic and reliable evidence to the response of glioblastoma to therapy. Moreover, these models enable the fine-tuning of different tumor microenvironment conditions and facilitate studies on the effects of the tumor microenvironment on glioblastoma chemoresistance. This review outlines current knowledge on the essence of glioblastoma chemoresistance and describes the progress achieved by 3D biomimetic models. Moreover, comprehensive literature assessment regarding the influence of 3D culturing and microenvironment mimicking on glioblastoma gene expression and biological behavior is also provided. The contribution of the blood-brain barrier as well as the blood-tumor barrier to glioblastoma chemoresistance is also reviewed from the perspective of 3D biomimetic models. Finally, the role of mathematical models in predicting 3D glioblastoma behavior and drug response is elaborated. In the future, technological innovations along with mathematical simulations should create reliable 3D biomimetic systems for glioblastoma research that should facilitate the identification and possibly application in preclinical drug testing and precision medicine.
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Affiliation(s)
- Tijana Stanković
- Department of Neurobiology, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060, Belgrade, Serbia
| | - Teodora Ranđelović
- Tissue Microenvironment Lab (TME), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain; Institute for Health Research Aragon (IIS Aragón), Instituto de Salud Carlos III, Zaragoza, Spain
| | - Miodrag Dragoj
- Department of Neurobiology, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060, Belgrade, Serbia
| | - Sonja Stojković Burić
- Department of Neurobiology, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060, Belgrade, Serbia
| | - Luis Fernández
- Tissue Microenvironment Lab (TME), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain; Centro Investigación Biomédica en Red. Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Aragon 50018, Spain; Institute for Health Research Aragon (IIS Aragón), Instituto de Salud Carlos III, Zaragoza, Spain
| | - Ignacio Ochoa
- Tissue Microenvironment Lab (TME), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain; Centro Investigación Biomédica en Red. Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Aragon 50018, Spain; Institute for Health Research Aragon (IIS Aragón), Instituto de Salud Carlos III, Zaragoza, Spain
| | - Victor M Pérez-García
- Departamento de Matemáticas, E.T.S.I. Industriales and Instituto de Matemática Aplicada a la Ciencia y la Ingeniería (IMACI), Universidad de Castilla-La Mancha, Ciudad Real, 13071, Spain
| | - Milica Pešić
- Department of Neurobiology, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060, Belgrade, Serbia.
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Marinari E, Dutoit V, Nikolaev S, Vargas MI, Schaller K, Lobrinus JA, Dietrich PY, Tsantoulis P, Migliorini D. Clonal Evolution of a High-Grade Pediatric Glioma With Distant Metastatic Spread. NEUROLOGY-GENETICS 2021; 7:e561. [PMID: 33898738 PMCID: PMC8063622 DOI: 10.1212/nxg.0000000000000561] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 12/10/2020] [Indexed: 12/13/2022]
Abstract
Objective High-grade glioma (HGG) rarely spreads outside the CNS. To test the hypothesis that the lesions were metastases originating from an HGG, we sequenced the relapsing HGG and distant extraneural lesions. Methods We performed whole-exome sequencing of an HGG lesion, its local relapse, and distant lesions in bone and lymph nodes. Results Phylogenetic reconstruction and histopathologic analysis confirmed the common glioma origin of the secondary lesions. The mutational profile revealed an IDH1/2 wild-type HGG with an activating mutation in EGFR and biallelic focal loss of CDKN2A (9p21). In the metastatic samples and the local relapse, we found an activating PIK3CA mutation, further copy number gains in chromosome 7 (EGFR), and a putative pathogenic driver mutation in a canonical splice site of FLNA. Conclusions Our findings demonstrate tumor spread outside the CNS and identify potential genetic drivers of metastatic dissemination outside the CNS, which could be leveraged as therapeutic targets or potential biomarkers.
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Affiliation(s)
- Eliana Marinari
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Valerie Dutoit
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Sergey Nikolaev
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Maria-Isabel Vargas
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Karl Schaller
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Johannes Alexander Lobrinus
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Pierre-Yves Dietrich
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Petros Tsantoulis
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
| | - Denis Migliorini
- Center for Translational Research in Onco-Hematology (E.M., V.D., P.-Y.D., P.T., D.M.), University of Geneva, Department of Oncology, Geneva University Hospital, Geneva and Swiss Cancer Center Léman (SCCL); Genetic Core Facility (S.N.), Geneva University Hospital; Diagnostic Department, Neuroradiology Division, (M.-I.V.), Neurosurgery Service (K.S.), and Department of Pathology (J.A.L.), Geneva University Hospital, Geneva, Switzerland
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Safaee S, Fardi M, Hemmat N, Khosravi N, Derakhshani A, Silvestris N, Baradaran B. Silencing ZEB2 Induces Apoptosis and Reduces Viability in Glioblastoma Cell Lines. Molecules 2021; 26:molecules26040901. [PMID: 33572092 PMCID: PMC7916008 DOI: 10.3390/molecules26040901] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/29/2021] [Accepted: 02/03/2021] [Indexed: 11/24/2022] Open
Abstract
Background: Glioma is an aggressive type of brain tumor that originated from neuroglia cells, accounts for about 80% of all malignant brain tumors. Glioma aggressiveness has been associated with extreme cell proliferation, invasion of malignant cells, and resistance to chemotherapies. Due to resistance to common therapies, glioma affected patients’ survival has not been remarkably improved. ZEB2 (SIP1) is a critical transcriptional regulator with various functions during embryonic development and wound healing that has abnormal expression in different malignancies, including brain tumors. ZEB2 overexpression in brain tumors is attributed to an unfavorable state of the malignancy. Therefore, we aimed to investigate some functions of ZEB2 in two different glioblastoma U87 and U373 cell lines. Methods: In this study, we investigated the effect of ZEB2 knocking down on the apoptosis, cell cycle, cytotoxicity, scratch test of the two malignant brain tumor cell lines U87 and U373. Besides, we investigated possible proteins and microRNA, SMAD2, SMAD5, and miR-214, which interact with ZEB2 via in situ analysis. Then we evaluated candidate gene expression after ZEB2-specific knocking down. Results: We found that ZEB2 suppression induced apoptosis in U87 and U373 cell lines. Besides, it had cytotoxic effects on both cell lines and reduced cell migration. Cell cycle analysis showed cell cycle arrest in G0/G1 and apoptosis induction in U87 and U373 cell lines receptively. Also, we have found that SAMAD2/5 expression was reduced after ZEB2-siRNA transfection and miR-214 upregulated after transfection. Conclusions: In line with previous investigations, our results indicated a critical oncogenic role for ZEB2 overexpression in brain glioma tumors. These properties make ZEB2 an essential molecule for further studies in the treatment of glioma cancer.
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Affiliation(s)
- Sahar Safaee
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran; (S.S.); (M.F.); (N.H.); (N.K.); (A.D.)
| | - Masoumeh Fardi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran; (S.S.); (M.F.); (N.H.); (N.K.); (A.D.)
- Hematology Division, Immunology Department, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran
| | - Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran; (S.S.); (M.F.); (N.H.); (N.K.); (A.D.)
| | - Neda Khosravi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran; (S.S.); (M.F.); (N.H.); (N.K.); (A.D.)
| | - Afshin Derakhshani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran; (S.S.); (M.F.); (N.H.); (N.K.); (A.D.)
- IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
| | - Nicola Silvestris
- IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
- Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
- Correspondence: (N.S.); or (B.B.)
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran; (S.S.); (M.F.); (N.H.); (N.K.); (A.D.)
- Correspondence: (N.S.); or (B.B.)
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Marinho MAG, da Silva Marques M, Lettnin AP, de Souza Votto AP, de Moraes Vaz Batista Filgueira D, Horn AP. Interaction Between Near-Infrared Radiation and Temozolomide in a Glioblastoma Multiform Cell Line: A Treatment Strategy? Cell Mol Neurobiol 2021; 41:91-104. [PMID: 32236902 PMCID: PMC11448574 DOI: 10.1007/s10571-020-00835-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 03/24/2020] [Indexed: 02/08/2023]
Abstract
Photodynamic therapy (PDT) is a potential therapeutic modality against cancer, resulting from the interaction of a photosensitizer (PS) and radiation that generates damage to tumor cells. The use of near-infrared radiation (IR-A) is relevant because presents recognized biological effects, such as antioxidant, neuroprotective and antitumor effects. Glioblastoma is the most aggressive central nervous system (CNS) neoplasm with high proliferation and tissue invasion capacity and is resistant to radio and chemotherapy. Here, we evaluated in vitro the possible interaction of temozolomide (TMZ) with IR-A in a glioblastoma cell line (C6) and in a human keratinocyte cell line (HaCat) how non-tumor cell model, in an attempt to search for a new treatment strategy. The effects of TMZ, IR-A and the interaction between TMZ and IR-A was evaluated by viability exclusion with trypan blue. To perform the interaction experiments, we have chosen 10 μM TMZ and 4.5 J/cm2 of IR-A. From this, we evaluated cytotoxicity, cell proliferation, intracellular reactive oxygen species levels (ROS), as well as the process of cell migration and the P-gp and MRP-1 activity. Cell death mainly due to apoptosis, followed by necrosis, decreased cell proliferation, increased ROS levels, decreased cell migration and decreased P-gp and MRP1 activity were observed only when there was interaction between TMZ and IR-A in the C6 cell line. The interaction between TMZ and IR-A was not able to affect cell proliferation in the HaCat non-tumor cell line. Our results suggest that this interaction could be a promising approach and that in the future may serve as an antitumor strategy for PDT application.
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Affiliation(s)
- Marcelo Augusto Germani Marinho
- Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Av. Itália, Km 8, Rio Grande, RS, CEP 96210-900, Brazil.
- Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Rio Grande, RS, Brazil.
| | - Magno da Silva Marques
- Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Av. Itália, Km 8, Rio Grande, RS, CEP 96210-900, Brazil
- Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Rio Grande, RS, Brazil
| | - Aline Portantiolo Lettnin
- Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Av. Itália, Km 8, Rio Grande, RS, CEP 96210-900, Brazil
- Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Rio Grande, RS, Brazil
| | - Ana Paula de Souza Votto
- Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Av. Itália, Km 8, Rio Grande, RS, CEP 96210-900, Brazil
- Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Rio Grande, RS, Brazil
| | - Daza de Moraes Vaz Batista Filgueira
- Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Av. Itália, Km 8, Rio Grande, RS, CEP 96210-900, Brazil
- Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Rio Grande, RS, Brazil
| | - Ana Paula Horn
- Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Av. Itália, Km 8, Rio Grande, RS, CEP 96210-900, Brazil
- Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande-FURG, Rio Grande, RS, Brazil
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Oktay K, Yildirim DC, Acikalin A, Ozsoy KM, Cetinalp NE, Erman T. Extensive Extraneural Metastases of Cerebral Glioblastoma in a Pediatric Patient: An Extreme Case Report and Comprehensive Review of the Literature. Pediatr Neurosurg 2021; 56:300-305. [PMID: 33853073 DOI: 10.1159/000515348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 02/18/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Extraneural metastases of glioblastoma are very rare clinical entities, especially in pediatric patients. Because of their rarity, they can be confused with other pathological processes. CASE PRESENTATION We report a case of 16-year-old boy with extensive extraneural metastases of glioblastoma. Lung, liver, cervical lymph nodes, skin, and bone metastases were detected in the patient. CONCLUSION We describe the presentation, evaluation, and diagnosis of this rare condition with regard to pertinent literature.
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Affiliation(s)
- Kadir Oktay
- Department of Neurosurgery, Cukurova University School of Medicine, Adana, Turkey
| | - Dogu Cihan Yildirim
- Department of Neurosurgery, Cukurova University School of Medicine, Adana, Turkey
| | - Arbil Acikalin
- Department of Pathology, Cukurova University School of Medicine, Adana, Turkey
| | - Kerem Mazhar Ozsoy
- Department of Neurosurgery, Cukurova University School of Medicine, Adana, Turkey
| | - Nuri Eralp Cetinalp
- Department of Neurosurgery, Cukurova University School of Medicine, Adana, Turkey
| | - Tahsin Erman
- Department of Neurosurgery, Cukurova University School of Medicine, Adana, Turkey
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Zhu M, Bian Y, Jiang J, Lei T, Shu K. Rapid screening for safety of donation from donors with central nervous system malignancies. Medicine (Baltimore) 2020; 99:e22808. [PMID: 33285676 PMCID: PMC7717844 DOI: 10.1097/md.0000000000022808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
With the increasing demand on organ transplants, it has become a common practice to include patients with primary central nervous system (CNS) malignancies as donors given the suggested low probability metastatic spread outside of the CNS. However, an extra-CNS spread of the disease cannot be excluded raising potential risks of cancer transmission from those donors. In order to balance between the risk of donor-derived disease transmission and the curative benefit for the recipient, a careful donor and organ selection is important. We performed a literature research and summarized all reported studies of organ transplants from donors suffered from primary CNS malignancies and determined the risk of tumor transmission to recipients. There were 22 cases of transplant-transmitted CNS tumors onto recipients since 1976. The association risks of cancer transmission were attributed to donor tumor histology, disruption of the blood-brain barrier, cerebrospinal fluid extra-CNS, and false diagnosis of primary intracranial tumor as well as the molecular properties of the primary tumor such as the existence of EGFR-amplification. The association risks and features of CNS tumors transmission recipients indicated that we need to reassess our thresholds for the potential fatal consequences of these donors.
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Affiliation(s)
| | | | - Jipin Jiang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China
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Abstract
Extraneural metastasis is extremely rare in pediatric patients with high-grade glioma and carries a grim prognosis. Detection of metastases at initial presentation is even rarer. A 15-year-old adolescent girl presented with paraplegia, urinary retention, and a constellation of systemic symptoms. Imaging showed a fourth ventricular lesion, innumerable intradural lesions, leptomeningeal seeding throughout the neuraxis, and numerous osteoblastic lesions involving the spine, ribs, sternum, pelvis, humerus, and femurs. Pathology confirmed metastatic diffuse midline glioma, H3K27M-mutant. Our patient died 2 weeks after initial presentation. Further work is needed to develop effective treatment strategies for these high-risk patients.
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Zhang J, Fang S, Song W, Zhang B, Fan W, Jin G, Liu F. Biological Characterization and Therapeutics for Subscalp Recurrent in Intracranial Glioblastoma. Onco Targets Ther 2020; 13:9085-9099. [PMID: 32982297 PMCID: PMC7498653 DOI: 10.2147/ott.s265322] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/28/2020] [Indexed: 01/01/2023] Open
Abstract
Purpose Gliomas are common intracranial tumors, of which 70% are malignant gliomas. Glioblastoma multiforme (GBM) is the most aggressive tumor, and patients with GBM have a median survival time of only 9–12 months; extracranial recurrence of GBM is very rare. A therapeutic strategy for this kind of recurrent tumor is lacking. Materials and Methods We present a case of a patient with extracranial recurrence of subscalp GBM. The subscalp tumor was resected and xenotransplanted into BALB/C nude mice. Then, glioma cells were isolated from the xenograft models and passaged in vitro. HE staining, immunohistochemistry, CCK-8 assays, karyotypic analysis, short tandem repeat STR analysis and flow cytometry were used to analyze the biological characteristics and malignant phenotype of these established cells. The cells and xenografts were then used as preclinical models to evaluate the antitumor efficacy of oncolytic herpes simplex virus 1 (oHSV-1). Results The isolated cells, which were named BT-01, were positive for Nestin and GFAP. The main characteristics of BT-01 cells were that they harbored glioblastoma stem-like cells (GSCs) and that they possessed highly aggressive migration capacities compared with the existing cell lines U87-MG and U251-MG. Moreover, BT-01 cells tolerated the chemotherapeutic drug temozolomide. Our study showed that oHSV-1 could replicate in and repress the growth of BT-01 cells and significantly inhibit tumor growth in xenograft models. Conclusion Taken together, our results showed that a new recurrent glioblastoma cell line was established, which can be useful for research on recurrent glioblastoma. We provided a reliable preclinical model to evaluate the antitumor efficacy of oHSV-1 in vivo and a promising therapy for recurrent GBM.
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Affiliation(s)
- Junwen Zhang
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
| | - Sheng Fang
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
| | - Wenjie Song
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
| | - Bo Zhang
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
| | - Wenhua Fan
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
| | - Guishan Jin
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
| | - Fusheng Liu
- Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China
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Alhoulaiby S, Abdulrahman A, Alouni G, Mahfoud M, Shihabi Z. Extra-CNS metastasis of glioblastoma multiforme to cervical lymph nodes and parotid gland: A case report. Clin Case Rep 2020; 8:1672-1677. [PMID: 32983474 PMCID: PMC7495837 DOI: 10.1002/ccr3.2985] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 03/02/2020] [Accepted: 05/12/2020] [Indexed: 11/25/2022] Open
Abstract
Extra CNS metastasis of glioblastoma multiforme is extremely rare. We report a case of a 53-year-old Caucasian male who, after undergoing surgical resection and nine months adjuvant therapy, had a recurrence of the cancer with an infiltration expanding outside the cranium to the left maxilla, mandible and parotid gland.
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Affiliation(s)
| | | | | | - Mufed Mahfoud
- Department of NeurosurgeryTishreen University hospitalLatakiaSyria
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