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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 -
Pediatric Blood & Cancer Jun 2020We report the outcomes of patients with pineoblastoma and trilateral retinoblastoma syndrome enrolled on the Head Start (HS) I-III trials.
BACKGROUND
We report the outcomes of patients with pineoblastoma and trilateral retinoblastoma syndrome enrolled on the Head Start (HS) I-III trials.
METHODS
Twenty-three children were enrolled prospectively between 1991 and 2009. Treatment included maximal surgical resection followed by five cycles of intensive chemotherapy and consolidation with marrow-ablative chemotherapy and autologous hematopoietic cell rescue (HDCx/AuHCR). Irradiation following consolidation was reserved for children over six years of age or those with residual tumor at the end of induction.
RESULTS
Median age was 3.12 years (range, 0.44-5.72). Three patients withdrew from the study treatment and two patients experienced chemotherapy-related death. Eight patients experienced progressive disease (PD) during induction chemotherapy and did not proceed to HDCx/AuHCR. Ten patients received HDCx/AuHCR; eight experienced PD post-consolidation. Seven patients received craniospinal irradiation (CSI) with a median dose of 20.7 Gy (range, 18-36 Gy) with boost(s) (median dose 27 Gy; range, 18-36 Gy); three received CSI as adjuvant therapy (two post-HDCx/AuHCR) and four upon progression/recurrence. The five-year progression-free survival (PFS) and overall survival (OS) were 9.7% (95% confidence intervals [CI]: 2.6%-36.0%) and 13% (95% CI: 4.5%-37.5%), respectively. Only three patients survived beyond five years. Favorable OS prognostic factors were CSI (hazard ratio [HR] = 0.30 [0.11-0.86], P = 0.025) and HDCx/AuHCR (HR = 0.40 [0.16-0.99], P = 0.047).
CONCLUSIONS
Within the HS I-III trials, CSI and HDCx/AuHCR were statistically associated with improved survival. The high PD rate during later induction cycles and following consolidation chemotherapy warrants consideration of fewer induction cycles prior to consolidation and the potential intensification of consolidation with multiple cycles of marrow-ablative chemotherapy and irradiation.
Topics: Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Infant; Male; Pineal Gland; Pinealoma; Prognosis; Prospective Studies; Survival Rate
PubMed: 32187454
DOI: 10.1002/pbc.28252 -
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 -
Neuro-oncology Aug 2011Central nervous system primitive neuroectodermal tumor (CNS PNET) and pineoblastoma are highly malignant embryonal brain tumors with poor prognoses. Current therapies...
Central nervous system primitive neuroectodermal tumor (CNS PNET) and pineoblastoma are highly malignant embryonal brain tumors with poor prognoses. Current therapies are based on the treatment of pediatric medulloblastoma, even though these tumors are distinct at both the anatomical and molecular level. CNS PNET and pineoblastoma have a worse clinical outcome than medulloblastoma; thus, improved therapies based on an understanding of the underlying biology of CNS PNET and pineoblastoma are needed. To this end, we characterized the genomic alterations of 36 pediatric CNS PNETs and 8 pineoblastomas using Affymetrix single nucleotide polymorphism arrays. Overall, the majority of CNS PNETs contained a greater degree of genomic imbalance than pineoblastomas, with gain of 19p (8 [27.6%] of 29), 2p (7 [24.1%] of 29), and 1q (6 [20.7%] of 29) common events in primary CNS PNETs. Novel gene copy number alterations were identified and corroborated by Genomic Identification of Significant Targets In Cancer (GISTIC) analysis: gain of PCDHGA3, 5q31.3 in 62.1% of primary CNS PNETs and all primary pineoblastomas and FAM129A, 1q25 in 55.2% of primary CNS PNETs and 50% of primary pineoblastomas. Comparison of our GISTIC data with publically available data for medulloblastoma confirmed these CNS PNET-specific copy number alterations. With use of the collection of 5 primary and recurrent CNS PNET pairs, we found that gain of 2p21 was maintained at relapse in 80% of cases. Novel gene copy number losses included OR4C12, 11p11.12 in 48.2% of primary CNS PNETs and 50% of primary pineoblastomas. Loss of CDKN2A/B (9p21.3) was identified in 14% of primary CNS PNETs and was significantly associated with older age among children (P = .05). CADPS, 3p14.2 was lost in 27.6% of primary CNS PNETs and was associated with poor prognosis (P = .043). This genome-wide analysis revealed the marked molecular heterogeneity of CNS PNETs and enabled the identification of novel genes and clinical associations potentially involved in the pathogenesis of these tumors.
Topics: Adolescent; Biomarkers, Tumor; Brain Neoplasms; Calcium-Binding Proteins; Child; Child, Preschool; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; DNA, Neoplasm; Female; Gene Expression Profiling; Genome, Human; Humans; Immunoenzyme Techniques; Infant; Male; Neoplasm Recurrence, Local; Neuroectodermal Tumors, Primitive; Oligonucleotide Array Sequence Analysis; Pineal Gland; Pinealoma; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Vesicular Transport Proteins
PubMed: 21798848
DOI: 10.1093/neuonc/nor070 -
Neurology India 2021Pineal parenchymal tumors account for less than 0.3% of all CNS tumors and "Pineal parenchymal tumor of intermediate differentiation" (PPTID; World Health Organization... (Review)
Review
BACKGROUND
Pineal parenchymal tumors account for less than 0.3% of all CNS tumors and "Pineal parenchymal tumor of intermediate differentiation" (PPTID; World Health Organization (WHO) grades II and III) exhibit intermediary differentiation and prognosis. However "Papillary tumor of the pineal region" (PTPR; WHO grades II and III) is a distinct entity.
OBJECTIVES
This combination of rarity and apparent similarity often leads to perplexity regarding the treatment and prognosis among neurosurgeons. In this review, we have tried to elucidate the differences in clinical as well as treatment modalities and outcomes of these two entities.
METHODS
We used the PubMed Database to search for all relevant articles using the keywords "pineal parenchymal tumor of intermediate differentiation" and "Papillary tumor of the pineal region." Articles having details regarding demographic and clinical variables along with treatment and outcomes were chosen for this study. Full text of these articles was analyzed, and data tabulated.
RESULTS
A total of 25 articles for PPTID and 45 for PTPR were found suitable for inclusion in this study. The studies were either case reports or small retrospective series with only one systemic review for each pathology. Despite the poor quality of data, some trends were apparent. Surgical resection offered a survival benefit in both pathologies. Radiotherapy was effective in increasing the survival in PPTID, while there was little to no effect in PPTR. Chemotherapy was not found to be beneficial in either.
CONCLUSION
Both of these tumors have moderate growth rate and potential for malignant behavior. This continuum of characteristics makes their optimal treatment strategy difficult and confusing. The discussion on comprehensive literature review should give information for neurosurgeons to decide on optimal treatment strategies.
Topics: Brain Neoplasms; Humans; Pineal Gland; Pinealoma; Prognosis; Retrospective Studies
PubMed: 34747779
DOI: 10.4103/0028-3886.329550 -
Turkish Neurosurgery 2015Primary pineal melanoma is a rare tumor. We herein review the histogenesis, pathology, radiology and therapeutic options of this rare tumor. (Review)
Review
AIM
Primary pineal melanoma is a rare tumor. We herein review the histogenesis, pathology, radiology and therapeutic options of this rare tumor.
MATERIAL AND METHODS
We conducted a PUBMED search using a combination of keywords such as "primary pineal melanoma", "CNS melanoma", and "pineal tumor" and identified 16 cases of primary pineal melanoma. Clinical features, pathologic characteristics and treatment details of these patients were noted from respective case reports. We also describe a case of a 45-year-old Indian woman with primary pineal melanoma treated with a combination of surgery and post-op radiation.
RESULTS
The median age at presentation is 50 years. Median duration of symptoms is 6 weeks. Common symptoms at presentation include headache (58.8%), personality changes (41.2%), gait disturbance (35.3%) and Parinaud's syndrome (29.4%). Surgery, radiotherapy and chemotherapy have been used in 29.4%, 47.1% and 23.5% of patients respectively. Median overall survival is 56 weeks. Leptomeningeal dissemination and ventricular ependymal spread were noted in 70.6% and 35.3% patients, respectively.
CONCLUSION
Combined modality treatment comprising maximal safe surgery and post-operative radiation should be preferred in patients with localized pineal melanoma without leptomeningeal dissemination. Taking a cue from other subsites of melanoma, chemotherapy can perhaps be deferred until recurrence.
Topics: Female; Humans; Melanoma; Middle Aged; Pinealoma
PubMed: 26014001
DOI: 10.5137/1019-5149.JTN.6568-12.1 -
Genome Research Feb 2023Pediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations in...
Pediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations in RB1 and DICER1, the role of epigenetic deregulation and -regulatory regions in PB pathogenesis and progression is largely unknown. Here, we generated genome-wide gene expression, chromatin accessibility, and H3K27ac profiles covering key time points of PB initiation and progression from pineal tissues of a mouse model of -driven PB. We identified PB-specific enhancers and super-enhancers, and found that in some cases, the accessible genome dynamics precede transcriptomic changes, a characteristic that is underexplored in tumor progression. During progression of PB, newly acquired open chromatin regions lacking H3K27ac signal become enriched for repressive state elements and harbor motifs of repressor transcription factors like HINFP, GLI2, and YY1. Copy number variant analysis identified deletion events specific to the tumorigenic stage, affecting, among others, the histone gene cluster and , the growth arrest specific gene. Gene set enrichment analysis and gene expression signatures positioned the model used here close to human PB samples, showing the potential of our findings for exploring new avenues in PB management and therapy. Overall, this study reports the first temporal and in vivo -regulatory, expression, and accessibility maps in PB.
Topics: Animals; Mice; Humans; Child; Chromatin; Pinealoma; Histones; Pineal Gland; Brain Neoplasms; Enhancer Elements, Genetic; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 36650051
DOI: 10.1101/gr.277037.122 -
Brain Tumor Research and Treatment Oct 2023This study aims to elucidate clinical features, therapeutic strategies, and prognosis of pineal parenchymal tumors (PPT) by analyzing a 30-year dataset of a single...
BACKGROUND
This study aims to elucidate clinical features, therapeutic strategies, and prognosis of pineal parenchymal tumors (PPT) by analyzing a 30-year dataset of a single institution.
METHODS
We reviewed data from 43 patients diagnosed with PPT at Seoul National University Hospital between 1990 and 2020. We performed survival analyses and assessed prognostic factors.
RESULTS
The cohort included 10 patients with pineocytoma (PC), 13 with pineal parenchymal tumor of intermediate differentiation (PPTID), and 20 with pineoblastoma (PB). Most patients presented with hydrocephalus at diagnosis. Most patients underwent an endoscopic third ventriculostomy and biopsy, with some undergoing additional resection after diagnosis confirmation. Radiotherapy was administered with a high prevalence of gamma knife radiosurgery for PC and PPTID, and craniospinal irradiation for PB. Chemotherapy was essential in the treatment of grade 3 PPTID and PB. The 5-year progression-free survival rates for PC, grade 2 PPTID, grade 3 PPTID, and PB were 100%, 83.3%, 0%, and 40%, respectively, and the 5-year overall survival rates were 100%, 100%, 40%, and 55%, respectively. High-grade tumor histology was associated with lower survival rates. Significant prognostic factors varied among tumor types, with World Health Organization (WHO) grade and leptomeningeal seeding (LMS) for PPTID, and the extent of resection and LMS for PB. Three patients experienced malignant transformations.
CONCLUSION
This study underscores the prognostic significance of WHO grades in PPT. It is necessary to provide specific treatment according to tumor grade. Grade 3 PPTID showed a poor prognosis. Potential LMS and malignant transformations necessitate aggressive multimodal treatment and close-interval screening.
PubMed: 37953449
DOI: 10.14791/btrt.2023.0033 -
Neurologia Medico-chirurgica Mar 1992Pineocytoma and pineoblastoma, originating from pineal parenchyma, are rare and usually solid. An unusual case of totally cystic pineocytoma in a 37-year-old female is...
Pineocytoma and pineoblastoma, originating from pineal parenchyma, are rare and usually solid. An unusual case of totally cystic pineocytoma in a 37-year-old female is reported. The tumor showed neuronal differentiation and had a good outcome. Prominent calcification associated with pineocytoma and pineoblastoma is an useful finding to differentiate these from benign pineal cysts.
Topics: Adult; Brain Neoplasms; Calcinosis; Cysts; Female; Humans; Pineal Gland; Pinealoma; Tomography, X-Ray Computed
PubMed: 1377802
DOI: 10.2176/nmc.32.169 -
Acta Neuropathologica Feb 2020Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the...
Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1-3 arose in older children (median ages 5.2-14.0 years) and had intermediate to excellent survival (5-year OS of 68.0-100%), while Group RB and MYC PB patients were much younger (median age 1.3-1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors.
Topics: Adolescent; Adult; Age Factors; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Male; MicroRNAs; Mutation; Pineal Gland; Pinealoma; Registries; Survival Rate; Young Adult
PubMed: 31820118
DOI: 10.1007/s00401-019-02111-y