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Progress in Neurological Surgery 2019Pineal region tumors represent a heterogeneous group of different histologic entities, for which the management can be a significant challenge, due to their critical... (Review)
Review
Pineal region tumors represent a heterogeneous group of different histologic entities, for which the management can be a significant challenge, due to their critical location and frequent aggressive behavior. Traditional management includes surgical resection, fractionated radiation therapy, and chemotherapy. Stereotactic radiosurgery (SRS) is being increasingly used in the treatment of these tumors. It is used as primary therapy for pineocytomas and papillary tumors of the pineal region, as an adjuvant radiation boost in combination with radiation or chemotherapy for pineoblastomas and germ cell tumors, or in the context of tumor recurrence. The reported morbidity is low, consisting in transient oculomotor disturbance in most cases. As a non-invasive alternative to microsurgical resection, SRS should always be considered when discussing these challenging cases.
Topics: Brain Neoplasms; Humans; Neoplasm Recurrence, Local; Pineal Gland; Pinealoma; Radiosurgery
PubMed: 31096261
DOI: 10.1159/000493062 -
Clinical Cancer Research : An Official... Jul 2017Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Approximately 40% of retinoblastomas are hereditary and due to germline mutations in the... (Review)
Review
Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Approximately 40% of retinoblastomas are hereditary and due to germline mutations in the gene. Children with hereditary RB are also at risk for developing a midline intracranial tumor, most commonly pineoblastoma. We recommend intensive ocular screening for patients with germline mutations for retinoblastoma as well as neuroimaging for pineoblastoma surveillance. There is an approximately 20% risk of developing second primary cancers among individuals with hereditary RB, higher among those who received radiotherapy for their primary RB tumors. However, there is not yet a clear consensus on what, if any, screening protocol would be most appropriate and effective. Neuroblastoma (NB), an embryonal tumor of the sympathetic nervous system, accounts for 15% of pediatric cancer deaths. Prior studies suggest that about 2% of patients with NB have an underlying genetic predisposition that may have contributed to the development of NB. Germline mutations in and account for most familial NB cases. However, other cancer predisposition syndromes, such as Li-Fraumeni syndrome, RASopathies, and others, may be associated with an increased risk for NB. No established protocols for NB surveillance currently exist. Here, we describe consensus recommendations on hereditary RB and NB from the AACR Childhood Cancer Predisposition Workshop. .
Topics: Anaplastic Lymphoma Kinase; Genetic Predisposition to Disease; Homeodomain Proteins; Humans; Neuroblastoma; Neuroimaging; Pinealoma; Receptor Protein-Tyrosine Kinases; Retinoblastoma; Retinoblastoma Binding Proteins; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 28674118
DOI: 10.1158/1078-0432.CCR-17-0652 -
Pediatric Neurosurgery 2023Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive... (Review)
Review
BACKGROUND
Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive multimodal treatment, the prognosis of many types is guarded, and treatment-related toxicity is significant. Recent advances in molecular diagnostics allowed the discovery of novel entities and inter-tumor subgroups, with opportunities for improved risk-stratification and treatment approaches.
SUMMARY
Medulloblastomas separate into four distinct subgroups with distinct clinicopathologic characteristics, and data from recent clinical trials for newly diagnosed medulloblastoma support subgroup-specific treatment approaches. Atypical teratoid rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and pineoblastoma, as well as other rare embryonal tumors, can be distinguished from histologically similar tumors by virtue of characteristic molecular findings, with DNA methylation analysis providing a strong adjunct in indeterminate cases. Methylation analysis can also allow further subgrouping of ATRT and pineoblastoma. Despite the dire need to improve outcomes for patients with these tumors, their rarity and lack of actionable targets lead to a paucity of clinical trials and novel therapeutics.
KEY MESSAGES
(1) Embryonal tumors can be accurately diagnosed with pediatric-specific sequencing techniques. (2) Medulloblastoma risk stratification and treatment decisions should take into account molecular subgroups. (3) There is a dire need for a novel collaborative clinical trial design to improve outcomes is rare pediatric embryonal tumors.
Topics: Child, Preschool; Humans; Infant; Brain Neoplasms; Central Nervous System Neoplasms; Cerebellar Neoplasms; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Pineal Gland; Pinealoma; Rhabdoid Tumor; Clinical Trials as Topic
PubMed: 37245504
DOI: 10.1159/000531256 -
Neuro-Chirurgie 2015The pineal gland has interested humans from millenniums. In this paper we review back in the history and the evolution of the pineal gland surgery. Originally, this... (Review)
Review
The pineal gland has interested humans from millenniums. In this paper we review back in the history and the evolution of the pineal gland surgery. Originally, this surgery used to carry a high rate of morbidity and mortality. Nowadays the development of the anesthetic, radiological, surgical and intensive care techniques have been responsible of an improvement of the surgical results and better quality of life. It is always interesting to know from where we come.
Topics: Biopsy; Brain Neoplasms; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, Ancient; Humans; Neurosurgical Procedures; Pineal Gland; Pinealoma; Quality of Life
PubMed: 25016433
DOI: 10.1016/j.neuchi.2013.03.005 -
Ochsner Journal 2019The pineal gland, a small, pinecone-shaped organ deep within the brain, is responsible for producing melatonin. The gland consists of pineal parenchymal cells and glial... (Review)
Review
The pineal gland, a small, pinecone-shaped organ deep within the brain, is responsible for producing melatonin. The gland consists of pineal parenchymal cells and glial cells that can form neoplasms. Pineal region neoplasms can also arise from germ cells and adjacent structures. This review focuses on detection of serum and cerebrospinal fluid (CSF) biomarkers of germ cell tumors and pineal parenchymal cell tumors, as these types comprise most neoplasms specific to the pineal region. For this review, we searched PubMed using the following keywords: biomarkers, germ cell tumor, germinoma, melatonin, pineal, pineal gland, pineal neoplasm, pinealoma, pineal parenchymal cell tumor, pineal region, and pineal tumor. We limited our search to full-text English articles and identified other relevant sources from the reference lists of identified articles. Serum and CSF biomarker assays have a role in cases of suspected pineal germ cell or parenchymal neoplasms. Biomarkers including alpha-fetoprotein, beta-human chorionic gonadotropin, and placental alkaline phosphatase inform diagnosis and treatment and are important for monitoring germ cell tumor response to treatment. No biomarkers are currently available that inform diagnosis or treatment of pineal parenchymal tumors, although melatonin assays may have a role in monitoring response to treatment. Serum and CSF biomarkers in conjunction with clinical and radiographic evidence of a pineal region mass can inform the decision whether to undertake stereotactic biopsy or surgical excision or whether to proceed straight to medical treatment.
PubMed: 30983898
DOI: 10.31486/toj.18.0110 -
Acta Ophthalmologica Feb 2022To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening.
METHODS
We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis.
RESULTS
Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs.
CONCLUSIONS
An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.
Topics: Brain Neoplasms; Early Diagnosis; Humans; Infant; Magnetic Resonance Imaging; Pineal Gland; Pinealoma; Retinal Neoplasms; Retinoblastoma
PubMed: 33939299
DOI: 10.1111/aos.14855 -
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 -
Advances in Experimental Medicine and... 2023Pineal region tumors fall into five broad categories: benign pineal region tumors, glial tumors, papillary tumors, pineal parenchymal tumors, and germ cell tumors....
Pineal region tumors fall into five broad categories: benign pineal region tumors, glial tumors, papillary tumors, pineal parenchymal tumors, and germ cell tumors. Genetic and transcriptional studies have identified key chromosomal alterations in germinomas (RUNDC3A, ASAH1, LPL) and in pineocytomas/pineoblastomas (DROSHA/DICER1, RB1). Pineal region tumors generally present with symptoms of hydrocephalus including nausea, vomiting, papilledema, and the classical Parinaud's triad of upgaze paralysis, convergence-retraction nystagmus, and light-near pupillary dissociation. Workup requires neuroimaging and tissue diagnosis via biopsy. In germinoma cases, diagnosis may be made based on serum or CSF studies for alpha-fetoprotein or beta-HCG making the preferred treatment radiosurgery, thereby preventing the need for unnecessary surgeries. Treatment generally involves three steps: CSF diversion in cases of hydrocephalus, biopsy through endoscopic or stereotactic methods, and open surgical resection. Multiple surgical approaches are possible for approach to the pineal region. The original approach to the pineal region was the interhemispheric transcallosal first described by Dandy. The most common approach is the supracerebellar infratentorial approach as it utilizes a natural anatomic corridor for access to the pineal region. The paramedian or lateral supracerebellar infratentorial approach is another improvement that uses a similar anatomic corridor but allows for preservation of midline bridging veins; this minimizes the chance for brainstem or cerebellar venous infarction. Determination of the optimal approach relies on tumor characteristics, namely location of deep venous structures to the tumor along with the lateral eccentricity of the tumor. The immediate post-operative period is important as hemorrhage or swelling can cause obstructive hydrocephalus and lead to rapid deterioration. Adjuvant therapy, whether chemotherapy or radiation, is based on tumor pathology. Improvements within pineal surgery will require improved technology for access to the pineal region along with targeted therapies that can effectively treat and prevent recurrence of malignant pineal region tumors.
Topics: Humans; Pinealoma; Pineal Gland; Brain Neoplasms; Glioma; Hydrocephalus; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37452938
DOI: 10.1007/978-3-031-23705-8_6 -
Neuro-Chirurgie 2015Pineal tumor management in pediatric patients must be based on close co-operation between oncologists, surgeons, radiation oncologists, neurologists, ophthalmologists,... (Review)
Review
Pineal tumor management in pediatric patients must be based on close co-operation between oncologists, surgeons, radiation oncologists, neurologists, ophthalmologists, and endocrinologists. Radiation therapy (RT) remains critical in most situations and should be assessed as soon as the diagnosis is made, in order to optimize the radiation technique. This paper will focus on RT modalities, indications, as well as modalities in main pediatric pineal tumors (germ cell tumors and pineal parenchyma tumors). RT modalities are presently being debated and new RT techniques (intensity-modulated RT, proton therapy etc.) that are now available for pineal lesions need to be evaluated. Radiation strategies are also controversial for germ cell tumors: cranio-spinal radiation versus chemotherapy followed by focal radiation, which also requires discussion.
Topics: Brain Neoplasms; Combined Modality Therapy; Humans; Neoplasms, Germ Cell and Embryonal; Pineal Gland; Pinealoma; Treatment Outcome
PubMed: 25612810
DOI: 10.1016/j.neuchi.2014.11.002 -
Neuro-Chirurgie 2015Germ cell tumors (GCTs) classically occur in gonads. However, they are the most frequent neoplasms in the pineal region. The pineal location of GCTs may be caused by the... (Review)
Review
Germ cell tumors (GCTs) classically occur in gonads. However, they are the most frequent neoplasms in the pineal region. The pineal location of GCTs may be caused by the neoplastic transformation of a primordial germ cell that has mismigrated. The World Health Organization (WHO) recognizes 5 histological types of intracranial GCTs: germinoma and non-germinomatous tumors including embryonal carcinoma, yolk sac tumor, choriocarcinoma and mature or immature teratoma. Germinomas and teratomas are frequently encountered as pure tumors whereas the other types are mostly part of mixed GCTs. In this situation, the neuropathologist has to be able to identify each component of a GCT. When diagnosis is difficult, use of recent immunohistochemical markers such as OCT(octamer-binding transcription factor)3/4, Glypican 3, SALL(sal-like protein)4 may be required. OCT3/4 is helpful in the diagnosis of germinomas, Glypican 3 in the diagnosis of yolk sac tumors and SALL4 in the diagnosis of the germ cell nature of an intracranial tumor. When the germ cell nature of a pineal tumor is doubtful, the finding of an isochromosome 12p suggests the diagnosis of GCT. The final pathological report should always be confronted with the clinical data, especially the serum or cerebrospinal fluid levels of β-human chorionic gonadotropin (HCG) and alpha-fetoprotein.
Topics: Biomarkers, Tumor; Brain Neoplasms; Glypicans; Humans; Neoplasms, Germ Cell and Embryonal; Pineal Gland; Pinealoma; Teratoma
PubMed: 24726316
DOI: 10.1016/j.neuchi.2013.06.006