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Cancer Radiotherapie : Journal de La... Sep 2023Rare central nervous system tumors are defined by an incidence rate of less than 6 cases per 100 000 individuals a year. It comprises a large panel of entities... (Review)
Review
Rare central nervous system tumors are defined by an incidence rate of less than 6 cases per 100 000 individuals a year. It comprises a large panel of entities including medulloblastoma, glioneuronal tumors, solitary fibrous tumors, rare pituitary tumors, ependymal or embryonal tumors. The management of these tumors is not clearly defined and radiotherapy indications should be discussed at a multidisciplinary board. Image-guided and intensity-modulated radiation therapy should be proposed and MRI has a fundamental place in the treatment preparation. To avoid the occurrence of side effects, proton therapy is playing an increasingly role for the treatment of these tumors.
Topics: Humans; Radiation Oncology; Proton Therapy; Radiotherapy, Intensity-Modulated; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 37481341
DOI: 10.1016/j.canrad.2023.06.008 -
Advances and Technical Standards in... 2024Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these... (Review)
Review
Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these tumors usually occur in childhood, they also rarely present in adult patients, either as a de novo diagnosis or as a delayed recurrence of a pediatric tumor in the setting of a patient that has transitioned into adult services.Due to the rarity of pediatric-like tumors in adults, the literature on these tumor types in adults is often limited to small case series, and treatment decisions are often based on the management plans taken from pediatric studies. However, the biology of these tumors is often different from the same tumors found in children. Likewise, adult patients are often unable to tolerate the side effects of the aggressive treatments used in children-for which there is little or no evidence of efficacy in adults. In this chapter, we review the literature and summarize the clinical, pathological, molecular profile, and response to treatment for the following pediatric tumor types-medulloblastoma, ependymoma, craniopharyngioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, germ cell tumors, choroid plexus tumors, midline glioma, and pleomorphic xanthoastrocytoma-with emphasis on the differences to the adult population.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Medulloblastoma; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 38592530
DOI: 10.1007/978-3-031-53578-9_5 -
Innere Medizin (Heidelberg, Germany) Jul 2024The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary... (Review)
Review
The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary microadenomas. The most common clinically relevant pituitary adenomas are prolactin-secreting, followed by HI, and far less common are growth hormone (GH)-, adrenocorticotropic hormone (ACTH)- and thyroid-stimulating hormone (TSH)-secreting adenomas. Pituitary adenomas are usually benign, although aggressive growth and invasion occurs in individual cases. Very rarely, they give rise to metastases and are then termed pituitary carcinomas. All pituitary tumors require endocrine testing for pituitary hormone excess. In addition to the medical history and clinical examination, laboratory diagnostics are very important. Symptoms such as irregular menstruation, loss of libido or galactorrhea often lead to the timely diagnosis of prolactinomas, and hyperprolactinemia can easily confirm the diagnosis (considering the differential diagnoses). Diagnosis is more difficult for all other hormone-secreting pituitary adenomas (acromegaly, Cushing's disease, TSHoma), as the symptoms are often non-specific (i.e., headaches, weight gain, fatigue, joint pain). Furthermore, comorbidities such as hypertension, diabetes, and depression are such widespread diseases that pituitary adenomas are rarely considered as the underlying cause. Timely diagnosis and appropriate treatment have a significant impact on morbidity, mortality, and quality of life. Therefore, the role of primary care physicians is very important for achieving an early diagnosis. In addition, patients with pituitary adenomas should always be referred to endocrinologists to ensure optimal diagnosis as well as treatment.
Topics: Humans; Pituitary Neoplasms; Diagnosis, Differential; Adenoma; Prolactinoma
PubMed: 38869654
DOI: 10.1007/s00108-024-01729-9 -
Best Practice & Research. Clinical... May 2024GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable... (Review)
Review
GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion.
Topics: Humans; Acromegaly; Pituitary Neoplasms; Neuroendocrine Tumors; MicroRNAs
PubMed: 38641464
DOI: 10.1016/j.beem.2024.101895 -
Neurosurgical Focus Aug 2023The objective of this review was to describe the immunological changes that take place in the dura mater in response to metastatic disease that seeds the CNS. The... (Review)
Review
OBJECTIVE
The objective of this review was to describe the immunological changes that take place in the dura mater in response to metastatic disease that seeds the CNS. The authors hypothesized that the dura's anatomy and resident immune cell population play a role in enabling metastasis to the brain and leptomeninges.
METHODS
An extensive literature search was conducted to identify evidence that supports the dura's participation in metastasis to the CNS. The authors' hypothesis was informed by a recent upsurge in studies that have investigated the dura's role in metastatic development, CNS infections, and autoimmunity. They reviewed this literature as well as the use of immunotherapy in treating brain metastases and how these therapies change the meningeal immune landscape to overcome and reverse tumor-promoting immunosuppression.
RESULTS
Evidence suggests that the unique architecture and immune cell profile of the dura, compared with other immune compartments within the CNS, facilitate entry of metastatic tumor cells into the brain. Once these tumor cells penetrate the dural barrier, they propagate an immunosuppressive tumor microenvironment. Therefore, immunotherapy may serve to overcome this immunosuppressive environment and liberate proinflammatory immune cells in an effort to combat metastatic disease.
CONCLUSIONS
Within the next few years, the authors expect the addition of several more scientific studies into the literature that further underscore the dura as a chief participant and neuroanatomical barrier in neuro-oncology.
Topics: Humans; Dura Mater; Brain Neoplasms; Brain; Supratentorial Neoplasms; Tumor Microenvironment
PubMed: 37527680
DOI: 10.3171/2023.5.FOCUS23229 -
JAMA Dec 2023
Topics: Humans; Adenoma; Pituitary Neoplasms; Prolactinoma
PubMed: 37948091
DOI: 10.1001/jama.2023.15248 -
Frontiers in Endocrinology 2023Pituitary neuroendocrine tumors (PitNETs), which originate from the pituitary gland, account for 10%-15% of all intracranial neoplasms. Recent studies have indicated...
BACKGROUND
Pituitary neuroendocrine tumors (PitNETs), which originate from the pituitary gland, account for 10%-15% of all intracranial neoplasms. Recent studies have indicated that enhancer RNAs (eRNAs) exert regulatory effects on tumor growth. However, the mechanisms underlying the eRNA-mediated tumorigenesis of PitNETs have not been elucidated.
METHODS
Normal pituitary and PitNETs tissues were used to identify the differentially expressed eRNAs (DEEs). Immune gene sets and hallmarks of cancer gene sets were quantified based on single sample gene set enrichment analysis (ssGSEA) algorithm using GSVA. The perspective of immune cells among all samples was calculated by the CIBERSORT algorithm. Moreover, the regulatory network composed of key DEEs, target genes of eRNAs, hallmarks of cancer gene sets, differentially expressed TF, immune cells and immune gene sets were constructed by Pearson correlation analysis. Small molecular anti-PitNETs drugs were explored by CMap analysis and the accuracy of the study was verified by and experiments, ATAC-seq and ChIP-seq.
RESULTS
In this study, data of 134 PitNETs and 107 non-tumorous pituitary samples were retrieved from a public database to identify differentially expressed genes. In total, 1128 differentially expressed eRNAs (DEEs) (494 upregulated eRNAs and 634 downregulated eRNAs) were identified. Next, the correlation of DEEs with cancer-related and immune-related gene signatures was examined to establish a co-expression regulatory network comprising 18 DEEs, 50 potential target genes of DEEs, 5 cancer hallmark gene sets, 2 differentially expressed transcription factors, 4 immune cell types, and 4 immune gene sets. Based on this network, the following four therapeutics for PitNETs were identified using Connectivity Map analysis: ciclopirox, bepridil, clomipramine, and alexidine. The growth-inhibitory effects of these therapeutics were validated using experiments. Ciclopirox exerted potential growth-inhibitory effects on PitNETs. Among the DEEs, , and were determined to be potential diagnostic and therapeutic biomarkers for PitNETs.
CONCLUSION
This study illustrated the significant influence of eRNAs on the occurrence and development of PitNETs. By constructing the co-expression regulation network, , and were identified as relatively significant DEEs which were considered as the novel biomarkers of diagnosis and treatment of PitNETs. This study demonstrated the roles of eRNAs in the occurrence and development of PitNETs and revealed that ciclopirox was a potential therapeutic for pituitary adenomas.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Ciclopirox; RNA; Transcription Factors; Pituitary Gland; Homeodomain Proteins
PubMed: 37534217
DOI: 10.3389/fendo.2023.1149997 -
European Journal of Endocrinology Dec 2023Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on...
BACKGROUND
Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma.
OBJECTIVE
We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas.
MATERIALS AND METHODS
A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically negative patients.
RESULTS
About 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant (LPV) in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18 was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas.
CONCLUSIONS
We did not identify any LPVs in patients over 30 years of age, either in a familial or in a sporadic context, and in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.
Topics: Male; Humans; Female; Adult; Prolactinoma; Cohort Studies; Retrospective Studies; Genetic Testing; Pituitary Neoplasms; Germ-Line Mutation
PubMed: 37956455
DOI: 10.1093/ejendo/lvad148 -
The Lancet. Diabetes & Endocrinology Mar 2024No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only... (Review)
Review
No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas.
Topics: Humans; Pituitary Neoplasms; Prospective Studies; Prognosis; Adenoma; Risk Factors
PubMed: 38301678
DOI: 10.1016/S2213-8587(23)00382-0 -
Journal of Neurosurgery Dec 2023Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however,...
OBJECTIVE
Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium.
METHODS
Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed.
RESULTS
A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade-i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival.
CONCLUSIONS
Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.
Topics: Humans; Meningioma; Meningeal Neoplasms; Mutation; Genomics; Supratentorial Neoplasms
PubMed: 37243548
DOI: 10.3171/2023.4.JNS222929