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Child's Nervous System : ChNS :... Oct 2023Pineal region tumors (PRTs) are tumors arising from the pineal gland and the paraspinal structures. These tumors are rare and heterogeneous that account for 2.8-10.1%... (Review)
Review
INTRODUCTION
Pineal region tumors (PRTs) are tumors arising from the pineal gland and the paraspinal structures. These tumors are rare and heterogeneous that account for 2.8-10.1% and 0.6-3.2% of tumors in children and in all ages, respectively. Almost all types and subtypes of CNS tumors may be diagnosed in this region. These tumors come from cells of the pineal gland (pinealocytes and neuroglial cells), ectopic primordial germ cells (PGC), and cells from adjacent structures. Hence, PRTs are consisted of pineal parenchyma tumors (PPTs), germ cell tumors (GCTs), neuroepithelial tumors (NETs), other miscellaneous types of tumors, cystic tumors (epidermoid, dermoid), and pineal cyst in addition. The symptoms of PRTs correlate to the increased intracranial cranial pressure due to obstructive hydrocephalus and dorsal midbrain compression. The diagnostic imaging studies are mainly MRI of brain (with and without gadolinium) along with a sagittal view of whole spine. Serum and/or CSF AFP/β-HCG helps to identify GCTs. The treatment of PRTs is consisted of the selection of surgical biopsy/resection, handling of hydrocephalus, neoadjuvant and/or adjuvant therapy according to age, tumor location, histopathological/molecular classification, grading of tumors, staging, and threshold value of markers (for GCTs) in addition.
METHODS
In this article, we review the following focus points: 1. Background of pineal region tumors. 2. Pineal GCTs and evolution of management. 3. Molecular study for GCTs and pineal parenchymal tumors. 4. Review of surgical approaches to the pineal region. 5. Contribution of endoscopy. 6. Adjuvant therapy (chemotherapy, radiotherapy, and combination). 7.
RESULTS
In all ages, the leading three types of PRTs in western countries were PPTs (22.7-34.8%), GCTs (27.3-34.4%), and NETs (17.2-28%). In children and young adults, the leading PRTs were invariably in the order of GCTs (40-80.5%), PPTs (7.6-21.6%), NETs (2.4-37.5%). Surgical biopsy/resection of PRTs is important for precision diagnosis and therapy. Safe resection with acceptable low mortality and morbidity was achieved after 1970s because of the advancement of surgical approaches, CSF shunt and valve system, microscopic and endoscopic surgery. Following histopathological diagnosis and classification of types and subtypes of PRTs, in PPTs, through molecular profiling, four molecular groups of pineoblastoma (PB) and their oncogenic driver were identified. Hence, molecular stratified precision therapy can be achieved.
CONCLUSION
Modern endoscopic and microsurgical approaches help to achieve precise histopathological diagnosis and molecular classification of different types and subtypes of pineal region tumors for risk-stratified optimal, effective, and protective therapy. In the future, molecular analysis of biospecimen (CSF and blood) along with AI radiomics on tumor imaging integrating clinical and bioinformation may help for personalized and risk-stratified management of patients with pineal region tumors.
Topics: Child; Young Adult; Humans; Pinealoma; Brain Neoplasms; Pineal Gland; Central Nervous System Neoplasms; Neoplasms, Germ Cell and Embryonal; Hydrocephalus
PubMed: 37831207
DOI: 10.1007/s00381-023-06081-1 -
Child's Nervous System : ChNS :... Sep 2023Histological and molecular characterization is essential for the diagnosis of pediatric brain tumors. In the pineal region tumors, it is necessary to remove a sufficient... (Review)
Review
Histological and molecular characterization is essential for the diagnosis of pediatric brain tumors. In the pineal region tumors, it is necessary to remove a sufficient tumor volume to make a diagnosis. However, surgery in this region is challenging due to its deep anatomical location and surrounded by critical structures and complex venous system. Knowledge of the anatomy and function of the pineal region and tumor histological types is imperative for the successful management of pineal region tumors. This article describes surgical approaches to pineal tumors, focusing on the occipital transtentorial approach and adding the author's experience to what has been known in the literature. Recent innovations have made this approach more popular and can be applied to occipital fossa lesions.
Topics: Child; Humans; Pinealoma; Brain Neoplasms; Pineal Gland; Neurosurgical Procedures
PubMed: 37436474
DOI: 10.1007/s00381-023-06071-3 -
Cancers Jun 2023Most of the literature on pineoblastoma consists of case reports and single-institution series. The goal of this systematic review and individual patient data (IPD)... (Review)
Review
Most of the literature on pineoblastoma consists of case reports and single-institution series. The goal of this systematic review and individual patient data (IPD) analysis was to summarize the existing literature, identify factors associated with overall survival (OS), and provide a contemporary update on prognosis for patients with pineoblastoma. Forty-four studies were identified with 298 patients having IPD. Kaplan-Meier analyses were used to report survival outcomes based on age, tumor metastases, extent of resection (EOR), adjuvant therapy, and publication year. Cox regression was performed to identify independent predictors of time to mortality. Multivariable recursive partitioning analysis was used to identify the most important subgroups associated with mortality. Patients were classified based on publication year before and after the last systematic review on this topic (pre-2012 and 2012 onwards) and compared using univariate and multivariable analyses. This study demonstrates that EOR less-than-gross total resection, metastatic presentation, adjuvant chemotherapy without radiation, and tumor presentation in children less than three years old are associated with poorer prognosis. Since 2012, the 5-year actuarial OS has improved from 32.8% to 56.1%, which remained significant even after accounting for EOR, age, and adjuvant therapy. Pineoblastoma remains a severe rare disease, but survival outcomes are improving.
PubMed: 37444483
DOI: 10.3390/cancers15133374 -
Child's Nervous System : ChNS :... Sep 2023Pineal parenchymal tumors in children are rare. They consist of two main types, pineoblastoma (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID),... (Review)
Review
Pineal parenchymal tumors in children are rare. They consist of two main types, pineoblastoma (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID), which are World Health Organization (WHO) grade 4 and grade 2-3 respectively. PBs are divided into four distinct molecular groups: PB-miRNA1, PB-miRNA2, PB-RB1, and PB-MYC/FOXR2. PB-RB1 and PB-MYC/FOXR2 affect young children and are associated with a dismal prognosis. PB-miRNA1 and PB-miRNA2 groups affect older children and follow a more favorable course. They are characterized by mutually exclusive alterations in genes involved in miRNA biogenesis, including DICER1, DROSHA, and DGCR8. They may be sporadic or may represent one manifestation of DICER1 syndrome. PB-RB1 tumors show alterations in the RB1 gene and may develop in the setting of congenital retinoblastoma, a condition known as "trilateral retinoblastoma." In the pediatric population, PPTIDs typically affect adolescents. They are characterized by small in-frame insertions in the KBTBD4 gene which is involved in ubiquitination.
Topics: Adolescent; Humans; Child; Child, Preschool; Pinealoma; Brain Neoplasms; Pineal Gland; Pathology, Molecular; Retinoblastoma; MicroRNAs; RNA-Binding Proteins; Retinal Neoplasms; Ribonuclease III; DEAD-box RNA Helicases; Forkhead Transcription Factors
PubMed: 35972537
DOI: 10.1007/s00381-022-05637-x -
Child's Nervous System : ChNS :... Sep 2023Surgical resection of pineal region tumors is challenging because of close proximity to the vein of Galen draining system and the quadrigeminal plate. Surgical resection...
PURPOSE
Surgical resection of pineal region tumors is challenging because of close proximity to the vein of Galen draining system and the quadrigeminal plate. Surgical resection usually is performed through the narrow corridor by piecemeal resection and en bloc resection is difficult in cases of large tumors. Moreover, in cases of hypervascular tumors, surgical resection through the narrow corridor could entail massive intraoperative bleeding. The effectiveness of neoadjuvant chemotherapy and second-look surgery for pineal region tumors for maximal safe resection was evaluated.
METHODS
Retrospective institutional review of pediatric patients with pineal region tumors who underwent second look surgery after neoadjuvant chemotherapy was performed.
RESULTS
Nine patients underwent surgical resection after neoadjuvant chemotherapy over the period of September 2017 to February 2022. The mean age was 7.7 years (ranged from 1.4 to 15.3 years). Three patients underwent partial resection via open craniotomy, and 6 underwent endoscopic biopsy as an initial surgery. The histopathological diagnoses were germ cell tumors in 5 patients (yolk sac tumors in 2, germinoma in 2, choriocarcinoma in 1), /rhabdoid tumor (AT/RT) in 2, medulloblastoma in 1, and high-grade glioneuronal tumor in 1. After several courses of chemotherapy, the second-look surgery was performed. The tumor volume was reduced in 8 patients (89%) after chemotherapy except for 1 case of growing teratoma syndrome. The tumor was extended laterally to the ambient cistern in 2 patients, and posteriorly to the tentorial surface of the cerebellum in 3 patients. The lesion was approached through occipital transtentorial approach in 8 patients and infratentorial supracerebellar approach in 1. Intraoperatively, the high vascularity of the tumor was not observed in all cases. Gross total resection (8 patients, 89%) or near total resection (1, 11%) was achieved in all cases. No complications were observed postoperatively in all cases. Eight patients subsequently underwent additional chemo-radiation therapy according to the initial diagnosis. All patients are alive with no evidence of recurrence with a mean follow-up of 33 months.
CONCLUSIONS
Neoadjuvant chemotherapy and second-look surgery for pediatric pineal region tumors was considered to be effective in reducing the tumor volume and vascularity, which facilitates the safe maximal tumor resection.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Second-Look Surgery; Retrospective Studies; Pinealoma; Brain Neoplasms; Pineal Gland; Cerebellar Neoplasms
PubMed: 36181520
DOI: 10.1007/s00381-022-05676-4 -
Clinical Radiology Jul 2023To differentiate between pineal germ cell tumour and pineoblastoma using apparent diffusion coefficient (ADC) values due to their overlapping imaging findings on...
AIM
To differentiate between pineal germ cell tumour and pineoblastoma using apparent diffusion coefficient (ADC) values due to their overlapping imaging findings on magnetic resonance imaging (MRI).
MATERIALS AND METHODS
This retrospective study was conducted on 33 patients with pineal germ cell tumours and eight patients with pineoblastoma who underwent pretreatment MRI. Twenty-seven patients (21 with pineal germ cell tumour and six with pineoblastoma) were included for ADC measurement. The minimum and mean ADC values of the tumours were measured, with normalized tumour to control ADC ratios generated. The MRI characteristics of the tumours were evaluated.
RESULTS
The mean and minimum ADC values, normalized mean and minimum ADC ratios of pineal germ cell tumours were significantly higher than those of pineoblastomas (all p<0.005). A cut-off value of 0.92 for the normalized mean ADC ratio was used to distinguish between pineal germ cell tumour and pineoblastoma and achieved an area under the curve of 0.95, sensitivity of 90.5%, specificity of 83.3%, and accuracy of 92.6%. An equal degree of contrast enhancement to the adjacent venous sinus was the only MRI characteristic that suggested the diagnosis of pineal germ cell tumour.
CONCLUSION
The ADC values could help differentiate between pineal germ cell tumour and pineoblastoma, specifically when conventional MRI findings are indeterminate.
Topics: Humans; Pinealoma; Brain Neoplasms; Retrospective Studies; Diffusion Magnetic Resonance Imaging; Diagnosis, Differential; Pineal Gland; Sensitivity and Specificity
PubMed: 37037704
DOI: 10.1016/j.crad.2023.03.008 -
Cancer Jul 2023Inhibition of the WEE1 kinase by adavosertib (AZD1775) potentiates replicative stress from genomic instability or chemotherapy. This study reports the pediatric solid...
BACKGROUND
Inhibition of the WEE1 kinase by adavosertib (AZD1775) potentiates replicative stress from genomic instability or chemotherapy. This study reports the pediatric solid tumor phase 2 results of the ADVL1312 trial combining irinotecan and adavosertib.
METHODS
Pediatric patients with recurrent neuroblastoma (part B), medulloblastoma/central nervous system embryonal tumors (part C), or rhabdomyosarcoma (part D) were treated with irinotecan and adavosertib orally for 5 days every 21 days. The combination was considered effective if there were at least three of 20 responses in parts B and D or six of 19 responses in part C. Tumor tissue was analyzed for alternative lengthening of telomeres and ATRX. Patient's prior tumor genomic analyses were provided.
RESULTS
The 20 patients with neuroblastoma (part B) had a median of three prior regimens and 95% had a history of prior irinotecan. There were three objective responses (9, 11, and 18 cycles) meeting the protocol defined efficacy end point. Two of the three patients with objective responses had tumors with alternative lengthening of telomeres. One patient with pineoblastoma had a partial response (11 cycles), but parts C and D did not meet the protocol defined efficacy end point. The combination was well tolerated and there were no dose limiting toxicities at cycle 1 or beyond in any parts of ADVL1312 at the recommended phase 2 dose.
CONCLUSION
This is first phase 2 clinical trial of adavosertib in pediatrics and the first with irinotecan. The combination may be of sufficient activity to consider further study of adavosertib in neuroblastoma.
Topics: Child; Humans; Irinotecan; Medulloblastoma; Neuroblastoma; Rhabdomyosarcoma; Cerebellar Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Protein-Tyrosine Kinases; Cell Cycle Proteins
PubMed: 37081608
DOI: 10.1002/cncr.34786 -
Frontiers in Oncology 2023The diencephalon is a complex midline structure consisting of the hypothalamus, neurohypophysis, subthalamus, thalamus, epithalamus, and pineal body. Tumors arising from... (Review)
Review
The diencephalon is a complex midline structure consisting of the hypothalamus, neurohypophysis, subthalamus, thalamus, epithalamus, and pineal body. Tumors arising from each of these diencephalic components differ significantly in terms of biology and prognosis. The aim of this comprehensive review is to describe the epidemiology, clinical symptoms, imaging, histology, and molecular markers in the context of the . We will also discuss the current management of each of these tumors.
PubMed: 37519792
DOI: 10.3389/fonc.2023.1180267 -
Child's Nervous System : ChNS :... Sep 2023
Topics: Child; Humans; Pinealoma; Brain Neoplasms; Pineal Gland
PubMed: 37332043
DOI: 10.1007/s00381-023-06031-x -
Journal of Pineal Research Dec 2023Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma... (Review)
Review
Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.
Topics: Humans; Pinealoma; Radiosurgery; Brain Neoplasms; Melatonin; Pineal Gland; Glioma; Neoplasms, Germ Cell and Embryonal
PubMed: 37705383
DOI: 10.1111/jpi.12910