Diffuse midline glioma (DMG), hitherto known as diffuse intrinsic pontine glioma (DIPG), is a rare and aggressive form of brain cancer that primarily affects children. Although the exact cause of DMG/DIPG is not known, a large proportion of DMG/DIPG tumors harbor mutations in the gene encoding the histone H3 protein, specifically the H3K27M mutation. This mutation decreases the level of H3K27me3, a histone modification that plays a vital role in regulating gene expression through epigenetic regulation. The mutation also alters the function of polycomb repressive complex 2 (PRC2), thereby preventing the repression of genes associated with cancer development. The decrease in H3K27me3 caused by the histone H3 mutation is accompanied by an increase in the level of H3K27ac, a post-translational modification related to active transcription. Dysregulation of histone modification markedly affects gene expression, contributing to cancer development and progression by promoting uncontrolled cell proliferation, tumor growth, and metabolism. DMG/DIPG alters the metabolism of methionine and the tricarboxylic acid cycle, as well as glucose and glutamine uptake. The role of epigenetic and metabolic changes in the development of DMG/DIPG has been studied extensively, and understanding these changes is critical to developing therapies targeting these pathways. Studies are currently underway to identify new therapeutic targets for DMG/DIPG, which may lead to the development of effective treatments for this devastating disease.
{"title":"Epigenetic and Metabolic Changes in Diffuse Intrinsic Pontine Glioma.","authors":"Jiyoon Park, Chan Chung","doi":"10.14791/btrt.2023.0011","DOIUrl":"https://doi.org/10.14791/btrt.2023.0011","url":null,"abstract":"<p><p>Diffuse midline glioma (DMG), hitherto known as diffuse intrinsic pontine glioma (DIPG), is a rare and aggressive form of brain cancer that primarily affects children. Although the exact cause of DMG/DIPG is not known, a large proportion of DMG/DIPG tumors harbor mutations in the gene encoding the histone H3 protein, specifically the H3K27M mutation. This mutation decreases the level of H3K27me3, a histone modification that plays a vital role in regulating gene expression through epigenetic regulation. The mutation also alters the function of polycomb repressive complex 2 (PRC2), thereby preventing the repression of genes associated with cancer development. The decrease in H3K27me3 caused by the histone H3 mutation is accompanied by an increase in the level of H3K27ac, a post-translational modification related to active transcription. Dysregulation of histone modification markedly affects gene expression, contributing to cancer development and progression by promoting uncontrolled cell proliferation, tumor growth, and metabolism. DMG/DIPG alters the metabolism of methionine and the tricarboxylic acid cycle, as well as glucose and glutamine uptake. The role of epigenetic and metabolic changes in the development of DMG/DIPG has been studied extensively, and understanding these changes is critical to developing therapies targeting these pathways. Studies are currently underway to identify new therapeutic targets for DMG/DIPG, which may lead to the development of effective treatments for this devastating disease.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/05/btrt-11-86.PMC10172016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diffuse intrinsic pontine gliomas (DIPGs) account for 10%-20% of all central nervous system tumors in children and are the leading cause of death in children with brain tumors. Although many clinical trials have been conducted over the past decades, the survival outcome has remained unchanged. Over 90% of children die within 2 years of the diagnosis, and radiotherapy remains the standard treatment to date. To improve the prognosis, hyperfractionated and hypofractionated radiotherapy and/or addition of radiosensitizers have been investigated. However, none of the radiotherapy approaches have shown a survival benefit, and the overall survival of patients with DIPG is approximately 11 months. Here, we comprehensively review the management of DIPG with focus on radiotherapy.
{"title":"Radiotherapy for Diffuse Intrinsic Pontine Glioma: Insufficient but Indispensable.","authors":"Hyun Ju Kim, Chang-Ok Suh","doi":"10.14791/btrt.2022.0041","DOIUrl":"https://doi.org/10.14791/btrt.2022.0041","url":null,"abstract":"<p><p>Diffuse intrinsic pontine gliomas (DIPGs) account for 10%-20% of all central nervous system tumors in children and are the leading cause of death in children with brain tumors. Although many clinical trials have been conducted over the past decades, the survival outcome has remained unchanged. Over 90% of children die within 2 years of the diagnosis, and radiotherapy remains the standard treatment to date. To improve the prognosis, hyperfractionated and hypofractionated radiotherapy and/or addition of radiosensitizers have been investigated. However, none of the radiotherapy approaches have shown a survival benefit, and the overall survival of patients with DIPG is approximately 11 months. Here, we comprehensively review the management of DIPG with focus on radiotherapy.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/d0/btrt-11-79.PMC10172015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shin Jung, In-Young Kim, Kyung-Sub Moon, Tae-Young Jung, Woo-Youl Jang, Yeong Jin Kim, Tae-Kyu Lee, Sue Jee Park, Sa-Hoe Lim
The paper provides a comprehensive overview of the growth and development of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital over the past 18 years. As the first brain tumor center in Korea when it was established in April 2004, Hwasun Neurosurgery has since become one of the leading institutions in brain tumor education and research in the country. Its impressive clinical and basic research capabilities, dedication to professional education, and numerous academic achievements have all contributed to its reputation as a top-tier institution. We hope this will become a useful guide for other brain tumor centers or educational institutions by sharing the story of Hwasun Neurosurgery.
{"title":"Distinct Specialized Center of Excellence, the Story of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital.","authors":"Shin Jung, In-Young Kim, Kyung-Sub Moon, Tae-Young Jung, Woo-Youl Jang, Yeong Jin Kim, Tae-Kyu Lee, Sue Jee Park, Sa-Hoe Lim","doi":"10.14791/btrt.2023.0005","DOIUrl":"https://doi.org/10.14791/btrt.2023.0005","url":null,"abstract":"<p><p>The paper provides a comprehensive overview of the growth and development of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital over the past 18 years. As the first brain tumor center in Korea when it was established in April 2004, Hwasun Neurosurgery has since become one of the leading institutions in brain tumor education and research in the country. Its impressive clinical and basic research capabilities, dedication to professional education, and numerous academic achievements have all contributed to its reputation as a top-tier institution. We hope this will become a useful guide for other brain tumor centers or educational institutions by sharing the story of Hwasun Neurosurgery.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/c2/btrt-11-94.PMC10172013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles E Mackel, Eduardo E Orrego-Gonzalez, Rafael A Vega
Music experience and creation is a complex phenomenon that involves multiple brain structures. Music mapping during awake brain surgery, in addition to standard speech and motor mapping, remains a controversial topic. Music function can be impaired selectively, despite overlap with other neural networks commonly tested during direct cortical stimulation. We describe the case of a 34-year-old male patient presenting with a glioma located within eloquent cortex, who is also a professional musician and actor. We performed an awake craniotomy (AC) that mapped the standard motor and speech areas, while the patient played guitar intraoperatively and sang. Outcomes were remarkable with preservation of function and noted improvements in his musical abilities in outpatient follow-up. In addition, we performed a review of the literature in which awake craniotomies were performed for the removal of brain tumors in patients with some background in music (e.g., score reading, humming/singing). To date, only 4 patients have played a musical instrument intraoperatively during an AC for brain tumor resection. Using awake cortical mapping techniques and paradigms for preserving speech function during an intraoperative musical performance with singing is feasible and can yield a great result for patients. The use of standard brain mapping over music processing mapping did not yield a negative outcome. More experience is needed to understand and standardize this procedure as the field of brain mapping continues to grow for tumor resections.
{"title":"Awake Craniotomy and Intraoperative Musical Performance for Brain Tumor Surgery: Case Report and Literature Review.","authors":"Charles E Mackel, Eduardo E Orrego-Gonzalez, Rafael A Vega","doi":"10.14791/btrt.2023.0002","DOIUrl":"https://doi.org/10.14791/btrt.2023.0002","url":null,"abstract":"<p><p>Music experience and creation is a complex phenomenon that involves multiple brain structures. Music mapping during awake brain surgery, in addition to standard speech and motor mapping, remains a controversial topic. Music function can be impaired selectively, despite overlap with other neural networks commonly tested during direct cortical stimulation. We describe the case of a 34-year-old male patient presenting with a glioma located within eloquent cortex, who is also a professional musician and actor. We performed an awake craniotomy (AC) that mapped the standard motor and speech areas, while the patient played guitar intraoperatively and sang. Outcomes were remarkable with preservation of function and noted improvements in his musical abilities in outpatient follow-up. In addition, we performed a review of the literature in which awake craniotomies were performed for the removal of brain tumors in patients with some background in music (e.g., score reading, humming/singing). To date, only 4 patients have played a musical instrument intraoperatively during an AC for brain tumor resection. Using awake cortical mapping techniques and paradigms for preserving speech function during an intraoperative musical performance with singing is feasible and can yield a great result for patients. The use of standard brain mapping over music processing mapping did not yield a negative outcome. More experience is needed to understand and standardize this procedure as the field of brain mapping continues to grow for tumor resections.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/5a/btrt-11-145.PMC10172011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min-Sung Kim, Se-Il Go, Chan Woo Wee, Min Ho Lee, Seok-Gu Kang, Kyeong-O Go, Sae Min Kwon, Woohyun Kim, Yun-Sik Dho, Sung-Hye Park, Youngbeom Seo, Sang Woo Song, Stephen Ahn, Hyuk-Jin Oh, Hong In Yoon, Sea-Won Lee, Joo Ho Lee, Kyung Rae Cho, Jung Won Choi, Je Beom Hong, Kihwan Hwang, Chul-Kee Park, Do Hoon Lim
Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period.
Methods: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed.
Results: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count.
Conclusion: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.
{"title":"The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1).","authors":"Min-Sung Kim, Se-Il Go, Chan Woo Wee, Min Ho Lee, Seok-Gu Kang, Kyeong-O Go, Sae Min Kwon, Woohyun Kim, Yun-Sik Dho, Sung-Hye Park, Youngbeom Seo, Sang Woo Song, Stephen Ahn, Hyuk-Jin Oh, Hong In Yoon, Sea-Won Lee, Joo Ho Lee, Kyung Rae Cho, Jung Won Choi, Je Beom Hong, Kihwan Hwang, Chul-Kee Park, Do Hoon Lim","doi":"10.14791/btrt.2023.0010","DOIUrl":"https://doi.org/10.14791/btrt.2023.0010","url":null,"abstract":"<p><strong>Background: </strong>During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period.</p><p><strong>Methods: </strong>The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed.</p><p><strong>Results: </strong>The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (<i>IDH</i>)-mutant and oligodendroglioma with <i>IDH</i>-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated <i>MGMT</i> promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count.</p><p><strong>Conclusion: </strong>It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/38/btrt-11-133.PMC10172008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles E Mackel, Harry Rosenberg, Hemant Varma, Erik J Uhlmann, Rafael A Vega, Ron L Alterman
Background: Cerebral chondrosarcoma metastases are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. We further present the first case with Maffucci syndrome.
Methods: Three databases, PubMed, Embase, and Google Scholar, and crossed references were queried for cerebral chondrosarcoma metastases. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analyses were performed.
Results: Fifty-six patients were included from 1,489 literature results. The average age at brain metastasis was 46.6±17.6 years and occurred at a median of 24±2.8 months from primary diagnosis. Primary tumor histology (dedifferentiated 5.0±1.5 months, mesenchymal 24±3.0 months, conventional 41±7.4 months, p<0.05) and grade (low grade 54±16.7 months vs. high-grade 10±6.4 months, p<0.001) correlated with time interval until brain metastasis. A multiple enchondromatosis syndrome occurred in 13.2% of cases. At time of brain metastases diagnosis, extracranial metastases were identified in 76.2% of cases. Median survival after the development of brain metastasis was 2.0±0.78 months with a 1-year survival of 10.0%. On regression analysis, surgery reduced brain metastasis mortality risk and radiation trended towards reduced mortality risk (surgery: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.064-0.763, p=0.017; radiation: HR 0.31, 95% CI 0.091-1.072, p=0.064).
Conclusion: We present a systematic review of cerebral chondrosarcoma metastases. Primary tumor histology and grade correlate with time until cerebral metastasis. Following cerebral metastasis, these tumors have poor prognosis and modestly benefit from surgery.
背景:脑软骨肉瘤转移是一种罕见的侵袭性肿瘤。罕见的表现妨碍了对诊断、危险因素、治疗和生存的严格分析。我们通过详尽的文献回顾分析了每一个报告的病例。我们进一步提出第一例马夫奇综合征。方法:检索PubMed、Embase、Google Scholar 3个数据库和交叉参考文献,查找脑软骨肉瘤转移病例。提取的变量包括人口统计学、危险因素、肿瘤特征、干预措施和结果。进行单因素和多因素分析。结果:从1489篇文献结果中纳入56例患者。脑转移的平均年龄为46.6±17.6岁,发生时间中位数为24±2.8个月。原发肿瘤组织学(去分化5.0±1.5个月,间充质24±3.0个月,常规41±7.4个月,ppp=0.017;辐射:HR 0.31, 95% CI 0.091 ~ 1.072, p=0.064)。结论:我们对脑软骨肉瘤转移进行了系统回顾。原发肿瘤的组织学和分级与脑转移的时间有关。脑转移后,这些肿瘤预后差,手术获益不大。
{"title":"Intracranial Metastasis of Extracranial Chondrosarcoma: Systematic Review With Illustrative Case.","authors":"Charles E Mackel, Harry Rosenberg, Hemant Varma, Erik J Uhlmann, Rafael A Vega, Ron L Alterman","doi":"10.14791/btrt.2023.0003","DOIUrl":"https://doi.org/10.14791/btrt.2023.0003","url":null,"abstract":"<p><strong>Background: </strong>Cerebral chondrosarcoma metastases are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. We further present the first case with Maffucci syndrome.</p><p><strong>Methods: </strong>Three databases, PubMed, Embase, and Google Scholar, and crossed references were queried for cerebral chondrosarcoma metastases. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analyses were performed.</p><p><strong>Results: </strong>Fifty-six patients were included from 1,489 literature results. The average age at brain metastasis was 46.6±17.6 years and occurred at a median of 24±2.8 months from primary diagnosis. Primary tumor histology (dedifferentiated 5.0±1.5 months, mesenchymal 24±3.0 months, conventional 41±7.4 months, <i>p</i><0.05) and grade (low grade 54±16.7 months vs. high-grade 10±6.4 months, <i>p</i><0.001) correlated with time interval until brain metastasis. A multiple enchondromatosis syndrome occurred in 13.2% of cases. At time of brain metastases diagnosis, extracranial metastases were identified in 76.2% of cases. Median survival after the development of brain metastasis was 2.0±0.78 months with a 1-year survival of 10.0%. On regression analysis, surgery reduced brain metastasis mortality risk and radiation trended towards reduced mortality risk (surgery: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.064-0.763, <i>p</i>=0.017; radiation: HR 0.31, 95% CI 0.091-1.072, <i>p</i>=0.064).</p><p><strong>Conclusion: </strong>We present a systematic review of cerebral chondrosarcoma metastases. Primary tumor histology and grade correlate with time until cerebral metastasis. Following cerebral metastasis, these tumors have poor prognosis and modestly benefit from surgery.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/bb/btrt-11-103.PMC10172009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pituitary apoplexy (PA) is a clinical syndrome resulting from sudden hemorrhage and/or infarction of the pituitary gland. Recent reports documented the development of PA secondary to treatment with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer. A 52-year-old woman visited our emergency room with a severe headache, occurred 1 day prior. She underwent breast-conserving surgery for breast cancer 1 month prior. She was currently undergoing radiation and hormone therapy, consisting of leuprorelin. Brain contrast-enhanced MRI revealed a pituitary adenoma with internal hemorrhage in the sellar and suprasellar areas. Pachymeningeal enhancement was observed along the retroclival and bilateral frontal areas. The patient was diagnosed with PA and aseptic meningitis. The patient underwent total excision via transsphenoidal surgery 8 days after admission. The patient was pathologically diagnosed with a pituitary adenoma with necrosis. On immunochemical staining, the tumor was positive for follicle-stimulating hormone. The follow-up MRI revealed no evidence of residual tumor or an improved pachymeningeal enhancement. She is currently undergoing follow-up at the neurosurgery and endocrinology outpatient departments with no noted complications. In breast cancer patients receiving GnRH agonist therapy, PA may be rare complication.
{"title":"Pituitary Apoplexy After Leuprolide Therapy in a Breast Cancer Patient: A Case Report.","authors":"Jungbin Lee, Sun-Chul Hwang, Sung-Tae Park","doi":"10.14791/btrt.2023.0006","DOIUrl":"https://doi.org/10.14791/btrt.2023.0006","url":null,"abstract":"<p><p>Pituitary apoplexy (PA) is a clinical syndrome resulting from sudden hemorrhage and/or infarction of the pituitary gland. Recent reports documented the development of PA secondary to treatment with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer. A 52-year-old woman visited our emergency room with a severe headache, occurred 1 day prior. She underwent breast-conserving surgery for breast cancer 1 month prior. She was currently undergoing radiation and hormone therapy, consisting of leuprorelin. Brain contrast-enhanced MRI revealed a pituitary adenoma with internal hemorrhage in the sellar and suprasellar areas. Pachymeningeal enhancement was observed along the retroclival and bilateral frontal areas. The patient was diagnosed with PA and aseptic meningitis. The patient underwent total excision via transsphenoidal surgery 8 days after admission. The patient was pathologically diagnosed with a pituitary adenoma with necrosis. On immunochemical staining, the tumor was positive for follicle-stimulating hormone. The follow-up MRI revealed no evidence of residual tumor or an improved pachymeningeal enhancement. She is currently undergoing follow-up at the neurosurgery and endocrinology outpatient departments with no noted complications. In breast cancer patients receiving GnRH agonist therapy, PA may be rare complication.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/16/btrt-11-153.PMC10172007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meningiomas are the most common primary brain tumors in adults. The treatment of non-benign meningiomas remains a challenging task, and after the publication of the 2021 World Health Organization classification, the importance of molecular biological classification is emerging. In this article, we introduce the mechanisms of brain invasion in atypical meningioma and review the genetic factors involved along with epigenetic regulation. First, it is important to understand the three major steps for brain invasion of meningeal cells: 1) degradation of extracellular matrix by proteases, 2) promotion of tumor cell migration to resident cells by adhesion molecules, and 3) neovascularization and supporting cells by growth factors. Second, the genomic landscape of meningiomas should be analyzed by major categories, such as germline mutations in NF2 and somatic mutations in non-NF2 genes (TRAF7, KLF4, AKT1, SMO, and POLR2A). Finally, epigenetic alterations in meningiomas are being studied, with a focus on DNA methylation, histone modification, and RNA interference. Increasing knowledge of the molecular landscape of meningiomas has allowed the identification of prognostic and predictive markers that can guide therapeutic decision-making processes and the timing of follow-up.
{"title":"Brain Invasion and Trends in Molecular Research on Meningioma.","authors":"Kyeong-O Go, Young Zoon Kim","doi":"10.14791/btrt.2022.0044","DOIUrl":"https://doi.org/10.14791/btrt.2022.0044","url":null,"abstract":"<p><p>Meningiomas are the most common primary brain tumors in adults. The treatment of non-benign meningiomas remains a challenging task, and after the publication of the 2021 World Health Organization classification, the importance of molecular biological classification is emerging. In this article, we introduce the mechanisms of brain invasion in atypical meningioma and review the genetic factors involved along with epigenetic regulation. First, it is important to understand the three major steps for brain invasion of meningeal cells: 1) degradation of extracellular matrix by proteases, 2) promotion of tumor cell migration to resident cells by adhesion molecules, and 3) neovascularization and supporting cells by growth factors. Second, the genomic landscape of meningiomas should be analyzed by major categories, such as germline mutations in <i>NF2</i> and somatic mutations in non-<i>NF2</i> genes (<i>TRAF7</i>, <i>KLF4</i>, <i>AKT1</i>, <i>SMO</i>, and <i>POLR2A</i>). Finally, epigenetic alterations in meningiomas are being studied, with a focus on DNA methylation, histone modification, and RNA interference. Increasing knowledge of the molecular landscape of meningiomas has allowed the identification of prognostic and predictive markers that can guide therapeutic decision-making processes and the timing of follow-up.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/3d/btrt-11-47.PMC9911709.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10725979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Woo Hyeong Joe, Chang-Young Lee, Chang-Hyun Kim, Young San Ko, Sang Pyo Kim, Sae Min Kwon
Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.
{"title":"Breast Cancer to Meningioma: A Rare Case of Tumor-to-Tumor Metastasis.","authors":"Woo Hyeong Joe, Chang-Young Lee, Chang-Hyun Kim, Young San Ko, Sang Pyo Kim, Sae Min Kwon","doi":"10.14791/btrt.2022.0042","DOIUrl":"https://doi.org/10.14791/btrt.2022.0042","url":null,"abstract":"<p><p>Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/b2/btrt-11-73.PMC9911711.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain metastases (BMs) often occur in patients with lung cancer, breast cancer, and melanoma and are the leading cause of morbidity and mortality. The incidence of BM has increased with advanced neuroimaging and prolonged overall survival of cancer patients. With the advancement of local treatment modalities, including stereotactic radiosurgery and navigation-guided microsurgery, BM can be controlled long-term, even in cases with multiple lesions. However, radiation/chemotherapeutic agents are also toxic to the brain, usually irreversibly and cumulatively, and it remains difficult to completely cure BM. Thus, we must understand the molecular events that begin and sustain BM to develop effective targeted therapies and tools to prevent local and distant treatment failure. BM most often spreads hematogenously, and the blood-brain barrier (BBB) presents the first hurdle for disseminated tumor cells (DTCs) entering the brain parenchyma. Nevertheless, how the DTCs cross the BBB and settle on relatively infertile central nervous system tissue remains unknown. Even after successfully taking up residence in the brain, the unique tumor microenvironment is marked by restricted aerobic glycolysis metabolism and limited lymphocyte infiltration. Brain organotropism, certain phenotype of primary cancers that favors brain metastasis, may result from somatic mutation or epigenetic modulation. Recent studies revealed that exosome secretion from primary cancer or over-expression of proteolytic enzymes can "pre-condition" brain vasculoendothelial cells. The concept of the "metastatic niche," where resident DTCs remain dormant and protected from systemic chemotherapy and antigen exposure before proliferation, is supported by clinical observation of BM in patients clearing systemic cancer and experimental evidence of the interaction between cancer cells and tumor-infiltrating lymphocytes. This review examines extant research on the metastatic cascade of BM through the molecular events that create and sustain BM to reveal clues that can assist the development of effective targeted therapies that treat established BMs and prevent BM recurrence.
{"title":"Molecular Biology of Brain Metastases.","authors":"Ho-Shin Gwak","doi":"10.14791/btrt.2022.0045","DOIUrl":"https://doi.org/10.14791/btrt.2022.0045","url":null,"abstract":"<p><p>Brain metastases (BMs) often occur in patients with lung cancer, breast cancer, and melanoma and are the leading cause of morbidity and mortality. The incidence of BM has increased with advanced neuroimaging and prolonged overall survival of cancer patients. With the advancement of local treatment modalities, including stereotactic radiosurgery and navigation-guided microsurgery, BM can be controlled long-term, even in cases with multiple lesions. However, radiation/chemotherapeutic agents are also toxic to the brain, usually irreversibly and cumulatively, and it remains difficult to completely cure BM. Thus, we must understand the molecular events that begin and sustain BM to develop effective targeted therapies and tools to prevent local and distant treatment failure. BM most often spreads hematogenously, and the blood-brain barrier (BBB) presents the first hurdle for disseminated tumor cells (DTCs) entering the brain parenchyma. Nevertheless, how the DTCs cross the BBB and settle on relatively infertile central nervous system tissue remains unknown. Even after successfully taking up residence in the brain, the unique tumor microenvironment is marked by restricted aerobic glycolysis metabolism and limited lymphocyte infiltration. Brain organotropism, certain phenotype of primary cancers that favors brain metastasis, may result from somatic mutation or epigenetic modulation. Recent studies revealed that exosome secretion from primary cancer or over-expression of proteolytic enzymes can \"pre-condition\" brain vasculoendothelial cells. The concept of the \"metastatic niche,\" where resident DTCs remain dormant and protected from systemic chemotherapy and antigen exposure before proliferation, is supported by clinical observation of BM in patients clearing systemic cancer and experimental evidence of the interaction between cancer cells and tumor-infiltrating lymphocytes. This review examines extant research on the metastatic cascade of BM through the molecular events that create and sustain BM to reveal clues that can assist the development of effective targeted therapies that treat established BMs and prevent BM recurrence.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/5f/btrt-11-8.PMC9911708.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10725980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}