-
Acta Neuropathologica May 2021Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal...
Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked the power to integrate molecular and clinical findings. The different proposed molecular group structures also highlighted a need to reach consensus on a robust and relevant classification system. We performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical, and genomic features of patients and samples from these pineal tumor groups were annotated. Four clinically and biologically relevant consensus PB groups were defined: PB-miRNA1 (n = 96), PB-miRNA2 (n = 23), PB-MYC/FOXR2 (n = 34), and PB-RB1 (n = 25). A final molecularly distinct group, designated PPTID (n = 43), comprised histological PPTID and PBs. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual tumor groups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection, and metastatic status varied significantly among tumor groups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 or PB-RB1. Reduced-dose CSI was adequate for patients with average-risk, PB-miRNA1/2 disease. We systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease groups, laying the groundwork for future studies as well as routine use in tumor diagnostic classification and clinical trial stratification.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; DNA Methylation; Female; Genome-Wide Association Study; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pineal Gland; Pinealoma; Transcriptome; Young Adult
PubMed: 33619588
DOI: 10.1007/s00401-021-02284-5 -
Child's Nervous System : ChNS :... Dec 2020We present a consecutive case series and a systematic review of surgically treated pediatric PCs. We hypothesized that the symptomatic PC is a progressive disease with... (Review)
Review
INTRODUCTION
We present a consecutive case series and a systematic review of surgically treated pediatric PCs. We hypothesized that the symptomatic PC is a progressive disease with hydrocephalus at its last stage. We also propose that PC microsurgery is associated with better postoperative outcomes compared to other treatments.
METHODS
The systematic review was conducted in PubMed and Scopus. No clinical study on pediatric PC patients was available. We performed a comprehensive evaluation of the available individual patient data of 43 (22 case reports and 21 observational series) articles.
RESULTS
The review included 109 patients (72% females). Ten-year-old or younger patients harbored smaller PC sizes compared to older patients (p < 0.01). The pediatric PCs operated on appeared to represent a progressive disease, which started with unspecific symptoms with a mean cyst diameter of 14.5 mm, and progressed to visual impairment with a mean cyst diameter of 17.8 mm, and hydrocephalus with a mean cyst diameter of 23.5 mm in the final stages of disease (p < 0.001). Additionally, 96% of patients saw an improvement in their symptoms or became asymptomatic after surgery. PC microsurgery linked with superior gross total resection compared to endoscopic and stereotactic procedures (p < 0.001).
CONCLUSIONS
Surgically treated pediatric PCs appear to behave as a progressive disease, which starts with cyst diameters of approximately 15 mm and develops with acute or progressive hydrocephalus at the final stage. PC microneurosurgery appears to be associated with a more complete surgical resection compared to other procedures.
Topics: Brain Neoplasms; Central Nervous System Cysts; Child; Cysts; Female; Humans; Male; Microsurgery; Pineal Gland
PubMed: 32691194
DOI: 10.1007/s00381-020-04792-3 -
Child's Nervous System : ChNS :... Feb 2023Intracranial germ cell tumor (iGCT) is a rare disorder and often occurs during childhood and adolescence. iGCTs are frequently localized in pineal region and... (Review)
Review
INTRODUCTION
Intracranial germ cell tumor (iGCT) is a rare disorder and often occurs during childhood and adolescence. iGCTs are frequently localized in pineal region and hypothalamic-neurohypophyseal axis (HNA). In spite of well-established clinical and pathological entity, histogenesis of iGCTs remains unsettled. Current theories of histogenesis of iGCTs include germ cell theory (from primordial germ cells (PGCs) of aberrant migration) and stem cell theory (transformed embryonic stem (ES) cells). In order to comprehend the histogenesis, we revisit the origin, migration, and fate of the human PGCs, and their transformation processes to iGCT.
DISCUSSION
In "germ cell theory," transformation of ectopic PGCs to iGCT is complex and involves multiple transcription factors. Germinoma is derived from ectopic PGCs and is considered a prototype of all GCTs. Non-germinomatous germ cell tumors (NGGCTs) develop from more differentiated counterparts of embryonic and extra-embryonic tissues. However, there is a distinct genomic/epigenomic landscape between germinoma and NGGCT. ES cells transformed from ectopic PGCs through molecular dysregulation or de-differentiation may become the source of iGCT. "Stem cell theory" is transformation of endogenous ES cells or primitive neural stem cell to iGCTs. It supports histological diversity of NGGCTs because of ES cell's pluripotency. However, neural stem cells are abundantly present along the subependymal zone; therefore, it does not explain why iGCTs almost exclusively occur in pineal and HNA locations. Also, the vast difference of methylation status between germinoma and NGGCT makes it difficult to theorize all iGCTs derive from the common cellular linage.
CONCLUSION
Transformation of PGCs to ES cells is the most logical mechanism for histogenesis of iGCT. However, its detail remains an enigma and needs further investigations.
Topics: Adolescent; Humans; Brain Neoplasms; Neoplasms, Germ Cell and Embryonal; Germinoma; Embryonic Stem Cells
PubMed: 36595083
DOI: 10.1007/s00381-022-05808-w -
Frontiers in Bioscience (Landmark... Jan 2024The conceptualization of polycystic ovary syndrome (PCOS) has primarily focused on hormonal alterations driven by changes within the hypothalamus and ovarian granulosa... (Review)
Review
The conceptualization of polycystic ovary syndrome (PCOS) has primarily focused on hormonal alterations driven by changes within the hypothalamus and ovarian granulosa cells, with treatment by the contraceptive pill and weight loss. However, a growing body of data implicates wider systemic and central nervous system (CNS) changes in the pathoetiology and pathophysiology of PCOS, with consequent implications for targeted treatments. It is proposed that there is a significant role for night-time interactions of factors acting to regulate whether the rising level of cortisol over the night and during the morning cortisol awakening response (CAR) is able to induce the nuclear translocation of the glucocorticoid receptor (GR), thereby influencing how the immune and glial systems regulate cellular function in preparation for the coming day. Factors affording protection in PCOS also inhibit GR nuclear translocation including gut microbiome-derived butyrate, and pineal/local melatonin as well as melatonin regulated bcl2-associated athanogene (BAG)-1. A significant pathophysiological role in PCOS is attributed to the aryl hydrocarbon receptor (AhR), which shows heightened levels and activity in PCOS. The AhR is activated by ligands of many systemic processes, including white adipocyte-derived kynurenine, implicating obesity in the pathophysiological changes occurring in the hypothalamus and ovaries. AhR activation has consequences for the physiological function in the hypothalamic paraventricular nucleus, granulosa cells and adipocytes, partly mediated by AhR upregulation of the mitochondrial N-acetylserotonin/melatonin ratio, thereby decreasing melatonin availability whilst increasing local stress plasticity in the paraventricular nucleus. This article reviews in detail the wider systemic and CNS changes in PCOS highlighting interactions of local and pineal melatonergic pathway, gut microbiome-derived butyrate, white adipocyte-derived kynurenine, the hypothalamic paraventricular nucleus tanycytes/astrocytes, and the hypothalamus-pituitary-adrenal (HPA) axis driven glucocorticoid receptor activation in PCOS pathophysiology. This integrates a wide array of previously disparate data on the biological underpinnings of PCOS, including how PCOS associates with many other currently classified medical conditions, such as depression, bipolar disorder, type 1 diabetes mellitus and the autism spectrum. Numerous future research and treatment implications are detailed.
Topics: Female; Humans; Melatonin; Polycystic Ovary Syndrome; Hydrocortisone; Kynurenine; Receptors, Glucocorticoid; Central Nervous System; Butyrates
PubMed: 38287831
DOI: 10.31083/j.fbl2901024 -
Headache Sep 2022To illustrate the possibility of spontaneous involution of a pineal cyst, justifying an initial observation strategy in patients without evident mass effect. (Review)
Review
OBJECTIVE
To illustrate the possibility of spontaneous involution of a pineal cyst, justifying an initial observation strategy in patients without evident mass effect.
BACKGROUND
Pineal cysts are frequent radiological findings, with a reported overall prevalence from 0.6% to 40%. Historically, surgery has been reserved for patients with symptoms attributable to a mass effect of the cyst. Despite the high prevalence of pineal cysts, the clinical approach to patients with non-specific symptoms remains controversial.
METHODS
We report on the spontaneous involution of a large pineal cyst in a 26-year-old female who presented in our outpatient clinic with transient symptoms of headache and nausea. PubMed and Web of Science databases were scrutinized using a predefined search strategy in accordance with the Population, Intervention, Comparison and Outcome (PICO) set-up using "pineal cyst" and "surgery" as search terms. Only peer-reviewed publications were considered eligible. Titles and abstracts of 1513 manuscripts were screened for relevance. After excluding 1420 publications evaluating non-relevant pathology, the eligibility of the remaining 93 full-text records was further assessed and included if they reported patients with pineal cysts presenting with intractable symptoms without hydrocephalus or Parinaud syndrome, and if they documented on their symptomatology and clinical management.
CONCLUSION
Recent case series and reviews report favorable results of surgery in patients with pineal cysts but also a potentially high complication rate. However, the evidence offered by these reports is limited and a placebo effect cannot be ruled out. Therefore, surgery cannot be unequivocally advocated in these patients. Instead, an initial surveillance strategy is advocated. We concur with a previously propounded surveillance strategy of a single follow-up magnetic resonance imaging at 12 months. This case report demonstrates the importance of an initial observation strategy since pineal cysts may also show a spontaneous involution.
Topics: Adult; Brain Neoplasms; Central Nervous System Cysts; Cysts; Female; Humans; Hydrocephalus; Magnetic Resonance Imaging; Pineal Gland
PubMed: 36017961
DOI: 10.1111/head.14378 -
Schizophrenia Research Jun 2022Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin...
BACKGROUND
Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders.
METHODS
This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups.
RESULTS
Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups.
CONCLUSION
These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.
Topics: Atrophy; Central Nervous System Cysts; Humans; Magnetic Resonance Imaging; Pineal Gland; Psychotic Disorders; Schizophrenia
PubMed: 35487129
DOI: 10.1016/j.schres.2022.04.005 -
Advances and Technical Standards in... 2023Pediatric pineal region tumors consist of tumors of pineal gland origin and parapineal origin. The former are comprised of germ cell tumor (GCT) and pineal parenchymal...
Pediatric pineal region tumors consist of tumors of pineal gland origin and parapineal origin. The former are comprised of germ cell tumor (GCT) and pineal parenchymal tumor. The latter originate from the surrounding neural structures, such as the midbrain and thalamus; thus, they are often benign gliomas during childhood. Pineal region tumors often cause obstructive hydrocephalus, which is the main cause of presenting symptoms. Advanced imaging discloses precise location and extension of the tumor and associated anomalies such as hydrocephalous, dissemination, hemorrhage, etc. Hydrocephalus has been managed with CSF diversion, mostly using an endoscopic third ventriculostomy. Because of different treatment paradigms for each tumor type, histological confirmation is needed either through biopsy, tumor markers for GCTs, and/or surgical resection sampling. Radical resection of these tumors remains a challenge due to their deep-seated location and involvement of delicate neural and vascular structures. Comparison of common craniotomy approaches, occipital transtentorial (OT) and infratentorial supracerebellar (ITSC), is reviewed for their advantages and disadvantages. Surgical area exposure and blind spots are important factors for successful tumor removal. The surgical techniques and nuances that the author employs for tumor resection via a posterior interhemispheric transtentorial approach are presented.
PubMed: 37770689
DOI: 10.1007/978-3-031-36785-4_11 -
Journal of Neuro-oncology Jan 2024To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT).
PURPOSE
To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT).
METHODS
Prospectively collected data of three patients with pineal anlage tumor from Germany was combined with clinical details and treatment information from 17 published cases.
RESULTS
Overall, 20 cases of PAT were identified (3 not previously reported German cases, 17 cases from published reports). Age at diagnosis ranged from 0.3 to 35.0 (median: 3.2 ± 7.8) years. All but three cases were diagnosed before the age of three years. For three cases, metastatic disease at initial staging was described. All patients underwent tumor surgery (gross-total resection: 9, subtotal resection/biopsy: 9, extent of resection unknown: 2). 15/20 patients were alive at last follow-up. Median follow-up for 10/15 surviving patients with available follow-up and treatment data was 2.4 years (0.3-6.5). Relapse was reported for 3 patients within 0.8 years after diagnosis. Five patients died, 3 after relapse and 2 from early postoperative complications. Two-year-progression-free- and -overall survival were 65.2 ± 12.7% and 49.2 ± 18.2%, respectively. All 4 patients who received intensive chemotherapy including high-dose chemotherapy combined with radiotherapy (2 focal, 2 craniospinal [CSI]) had no recurrence. Focal radiotherapy- and CSI-free survival rates in 13 evaluable patients were 46.2% (6/13) and 61.5% (8/13), respectively.
CONCLUSION
PAT is an aggressive disease mostly affecting young children. Therefore, adjuvant therapy using intensive chemotherapy and considering radiotherapy appears to comprise an appropriate treatment strategy. Reporting further cases is crucial to evaluate distinct treatment strategies.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Young Adult; Brain Neoplasms; Neoplasm Recurrence, Local; Pineal Gland; Pinealoma; Recurrence; Supratentorial Neoplasms; Treatment Outcome
PubMed: 38253790
DOI: 10.1007/s11060-023-04547-5 -
Molecular Biology Reports May 2021Neuroblastoma is a deadly and serious malignancy among children. Although many developments have been occurred for the treatment of this disease, the rate of mortality... (Review)
Review
Neuroblastoma is a deadly and serious malignancy among children. Although many developments have been occurred for the treatment of this disease, the rate of mortality is still high. Therefore, it is necessary to search for novel complementary and alternative therapies. Melatonin, a hormone secreted from pineal gland, is a multifunctional agent having anticancer potentials. Recently, several investigations have been conducted indicating melatonin effects against neuroblastoma. In this paper, we summarize current evidence on anti-neuroblastoma effects of melatonin based on cellular pathways.
Topics: Antineoplastic Agents; Child, Preschool; Humans; Melatonin; Neuroblastoma; Pediatrics; Pineal Gland; Signal Transduction
PubMed: 34061325
DOI: 10.1007/s11033-021-06439-1 -
Journal of Neurosurgical Sciences Feb 2021Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management...
BACKGROUND
Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI.
METHODS
Eleven adult patients with pineal cysts (>1 cm) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. Phase contrast magnetic resonance imaging (PC-MRI) in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test.
RESULTS
Patients were 39±13 years (mean±SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; P=0.009). Volume of small cysts (4954±2157 mm) was significantly different compared to large cysts (13,752±3738 mm; P=0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 μL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 μL/cardiac cycle (P=0.008).
CONCLUSIONS
Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.
Topics: Adult; Brain Neoplasms; Cerebral Aqueduct; Child; Cysts; Female; Humans; Hydrocephalus; Magnetic Resonance Imaging
PubMed: 29480683
DOI: 10.23736/S0390-5616.18.04258-3