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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 -
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 -
Journal of Neuro-oncology Apr 2023Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare,...
PURPOSE
Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor.
METHODS
At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort.
RESULTS
PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation.
CONCLUSIONS
Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.
Topics: Humans; Male; Female; Middle Aged; Pinealoma; Brain Neoplasms; Cohort Studies; Progression-Free Survival; Pineal Gland; Retrospective Studies
PubMed: 37052748
DOI: 10.1007/s11060-023-04310-w -
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 -
Expert Review of Molecular Diagnostics Mar 2020: Embryonal brain tumors (EBTs) are highly aggressive malignancies predominantly affecting children. They include medulloblastoma (MB), atypical rhabdoid/teratoid tumors... (Review)
Review
: Embryonal brain tumors (EBTs) are highly aggressive malignancies predominantly affecting children. They include medulloblastoma (MB), atypical rhabdoid/teratoid tumors (ATRT), pineoblastoma (PB), embryonal tumor multiple rosettes (ETMR)/-altered tumors, and newly recognized embryonal tumors with activation or alteration.: This review will provide a comprehensive overview and updated of the literature on each of these EBTs. The evolution from location- and histopathology-based diagnosis to more specific and robust molecular-based classification schemes, as well as treatment modalities, will be discussed.: The subgrouping of EBTs with multi-omic profiling has had important implications for risk stratification and discovery of targetable driver pathways. However, these innovations are unlikely to significantly improve survival among high-risk patients until robust preclinical studies are conducted, followed by validation in biology-informed clinical trials.
Topics: Age Factors; Biomarkers, Tumor; Brain Neoplasms; Child; Diagnosis, Differential; Disease Management; Disease Susceptibility; Humans; Neoplasms, Germ Cell and Embryonal
PubMed: 31917601
DOI: 10.1080/14737159.2020.1714439 -
Neuro-oncology Advances 2022Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included...
BACKGROUND
Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain.
PATIENTS AND METHODS
Centrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher's exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses.
RESULTS
We describe a pooled cohort of 178 pineoblastoma cases from Children's Oncology Group (n = 82) and institutional series (n = 96) over 30 years. Children <3 years of age have significantly worse survival compared to older children, with 5-year progression-free survival (PFS) and overall survival (OS) estimates of 13.5 ± 5.1% and 16.2 ± 5.3%, respectively, compared with 60.8 ± 5.6% and 67.3 ± 5.0% for ≥3 years old (both < .0001). Multivariable analysis showed male sex was associated with worse PFS in children <3 years of age (hazard ratio [HR] 3.93, 95% CI 1.80-8.55; = .0006), suggestive of sex-specific risks needing future validation. For children ≥3 years of age, disseminated disease at diagnosis was significantly associated with an inferior 5-year PFS of 39.2 ± 9.7% (HR 2.88, 95% CI 1.52-5.45; = .0012) and 5-year OS of 49.8 ± 9.1% (HR 2.87, 95% CI 1.49-5.53; = .0016).
CONCLUSION
Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.
PubMed: 35664557
DOI: 10.1093/noajnl/vdac056 -
Problemy Endokrinologii Oct 2023DICER1 syndrome is a rare genetic disorder with the progressive development of malignant and non-malignant diseases in childhood. The cause of this syndrome is a... (Review)
Review
DICER1 syndrome is a rare genetic disorder with the progressive development of malignant and non-malignant diseases in childhood. The cause of this syndrome is a dusfunction of the endoribonuclease DICER, which plays an important role in the processing of microRNAs with subsequent regulation of the control of the expression of oncogenes and tumor suppressor genes. Clinical manifestations of dyseropathies is very different and may include both endocrine manifestations - multinodular goiter, differentiated thyroid cancers, ovarian stromal tumors, pituitary blastoma, and non-endocrine formations - pleuropulmonary blastoma, cystic nephroma, pineoblastoma. The presence of somatic mutations of the DICER1 gene is a resultant stage in the pathogenesis of dyseropathies, determining the further path of oncogenesis. At present, DICER1 syndrome is diagnosed extremely rarely, which leads to late detection of the components of the disease in the patient, late diagnosis of neoplasms, lack of family counseling. Diagnosis at the early stages of the disease, the development of screening programs for the management of these patients allows minimizing the risks of developing more malignant, aggressive forms of the disease.
Topics: Humans; Ribonuclease III; DEAD-box RNA Helicases; Mutation; Female; Thyroid Neoplasms; Goiter, Nodular; Pulmonary Blastoma
PubMed: 38796764
DOI: 10.14341/probl13383 -
Journal of Neurosurgery. Pediatrics Sep 2022DICER1-mutant malignant brain neoplasms are very rare tumors, and published data have relied on case reports or small case series. In this review, the authors aimed to... (Review)
Review
OBJECTIVE
DICER1-mutant malignant brain neoplasms are very rare tumors, and published data have relied on case reports or small case series. In this review, the authors aimed to systematically summarize the types and distribution patterns of DICER1 mutations, clinicopathological characteristics, and prognostic outcomes of these tumors.
METHODS
The authors searched PubMed and Web of Science for relevant studies. They included studies if they provided individual patient data of primary malignant brain tumors carrying DICER1 mutations.
RESULTS
The authors found 16 studies consisting of 9 embryonal tumors with multilayered rosettes (ETMRs), 30 pineoblastomas, 52 primary intracranial sarcomas, and 27 pituitary blastomas. Pineoblastoma, ETMR, and pituitary blastoma were more likely to carry DICER1 germline mutations, while only a small subset of primary intracranial sarcomas harbored these mutations (p < 0.001). Nearly 80% of tumors with germline mutations also had another somatic mutation in DICER1. ETMR and primary intracranial sarcoma were associated with an increased risk for tumor progression and relapse compared with pituitary blastoma and pineoblastoma (p = 0.0025), but overall survival (OS) was not significantly different. Gross-total resection (GTR) and radiotherapy administration were associated with prolonged OS.
CONCLUSIONS
ETMR, pineoblastoma, primary intracranial sarcoma, and pituitary blastoma should be considered rare phenotypes of the DICER1 syndrome, and families should be counseled and screened for associated tumors. ETMR and primary intracranial sarcoma had a higher risk of relapse. GTR and radiotherapy appeared to improve the OS of patients with DICER1-mutant malignant intracranial tumors.
PubMed: 35901678
DOI: 10.3171/2022.6.PEDS22119 -
Current Oncology Reports Jul 2018Malignant embryonal brain tumors (EBTs) of childhood span a wide clinical spectrum but can share remarkably similar morphologic features. This overlap presents... (Review)
Review
PURPOSE OF REVIEW
Malignant embryonal brain tumors (EBTs) of childhood span a wide clinical spectrum but can share remarkably similar morphologic features. This overlap presents significant diagnostic challenges, particularly for tumor entities that are rarely encountered in clinical practice and for which diagnostic criteria were poorly defined. This review will provide an update on the evolving characterization and treatment of rare EBTs.
RECENT FINDINGS
Rapid advances in genomic tools have led to the discovery of robust molecular markers, and identification of novel tumor types and subtypes for almost all major categories of pediatric brain tumors. These developments have had significant impact on improving the diagnostic classification of the rare EBTs, particularly for tumors with newly recognized C19MC alterations, central nervous system primitive neuroectodermal tumors (CNS-PNET), and pineoblastoma (PB). These important developments in the clinical and molecular understanding of rare EBTs are paving the way for novel therapeutic strategies and improved clinical management.
Topics: Brain Neoplasms; Disease Management; Humans; Neoplasms, Germ Cell and Embryonal; Prognosis; Rare Diseases
PubMed: 29995179
DOI: 10.1007/s11912-018-0717-7