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Cancers Jul 2022Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically... (Review)
Review
Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically heterogeneous group of tumors. Among these tumors, pineal parenchymal tumors and germ cell tumors (GCT) represent the most frequent types of lesions. According to the new WHO 2021 classification, pineal parenchymal tumors include five distinct histotypes: pineocytoma (PC), pineal parenchymal tumors of intermediate differentiation (PPTID), papillary tumor of the pineal region (PTPR), pinealoblastoma (PB), and desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant; GCTs include germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, mixed GCTs. Neuroradiological assessment has a pivotal role in the diagnostic work-up, surgical planning, and follow-up of patients with pineal masses. Surgery can represent the mainstay of treatment, ranging from biopsy to gross total resection, yet pineal region tumors associated with obstructive hydrocephalus may be surgically managed via ventricular internal shunt or endoscopic third ventriculostomy. Radiotherapy remains an essential component of the multidisciplinary treatment approach for most pineal region tumors; however, treatment volumes depend on the histological subtypes, grading, extent of disease, and the combination with chemotherapy. For localized germinoma, the current standard of care is chemotherapy followed by reduced-dose whole ventricular irradiation plus a boost to the primary tumor. For pinealoblastoma patients, postoperative radiation has been associated with higher overall survival. For the other pineal tumors, the role of radiotherapy remains poorly studied and it is usually reserved for aggressive (grade 3) or recurrent tumors. The use of systemic treatments mainly depends on histology and prognostic factors such as residual disease and metastases. For pinealoblastoma patients, chemotherapy protocols are based on various alkylating or platinum-based agents, vincristine, etoposide, cyclophosphamide and are used in association with radiotherapy. About GCTs, their chemosensitivity is well known and is based on cisplatin or carboplatin and may include etoposide, cyclophosphamide, or ifosfamide prior to irradiation. Similar regimens containing platinum derivatives are also used for non-germinomatous GCTs with very encouraging results. However, due to a greater understanding of the biology of the disease's various molecular subtypes, new agents based on targeted therapy are expected in the future. On behalf of the EURACAN domain 10 group, we reviewed the most important and recent developments in histopathological characteristics, neuro-radiological assessments, and treatments for pineal region tumors.
PubMed: 35954310
DOI: 10.3390/cancers14153646 -
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 -
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 -
Contrast Media & Molecular Imaging 2022Tumors in the pineal region are deep, with complex surrounding anatomy, adjacent to important blood vessels and nerve structures, and surgical resection is difficult and... (Review)
Review
Tumors in the pineal region are deep, with complex surrounding anatomy, adjacent to important blood vessels and nerve structures, and surgical resection is difficult and risky. In this paper, we reviewed the literature to understand the epidemiology and clinical manifestations of pineal region tumors in the country and study the clinical indications, related problems, and successful experiences of patients with pineal region tumors treated by the transtentorial-superior approach. The clinical data of 80 patients with pineal region tumors were selected as the retrospective research objects and divided into the control group and the treatment group, with 40 cases in each group, according to the random number table method. The control group was treated using the endoscopic transtentorial approach (Poppen approach), while the treatment group was treated with the endoscopic supratentorial approach (Krause approach). The inflammatory factors, inflammatory stress response, postoperative neurological dysfunction, clinical efficacy, and poor prognosis were observed and compared between the two groups. Tumor resection and recurrence were used to compare the clinical outcomes of tumors in the pineal region. The extent of surgical resection was 100% higher in both groups, and the treatment group was comparable to the control group. The prognosis of patients after the operation was poor. Nausea and vomiting, visual disturbance, upper vision paralysis, and ataxia in the treatment group were significantly lower than those in the control group, with no statistical significance ( > 0.05). At the same time, the bone window can be reduced to reduce trauma and provide a certain reference for patients to choose a safe and complete resection method.
Topics: Brain Neoplasms; Case-Control Studies; Cerebellum; Humans; Pineal Gland; Pinealoma; Retrospective Studies; Treatment Outcome
PubMed: 36017015
DOI: 10.1155/2022/5702309 -
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 -
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 -
World Neurosurgery Mar 2022Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated... (Review)
Review
BACKGROUND
Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases.
METHODS
PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed.
RESULTS
We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P < 0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence.
CONCLUSIONS
Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.
Topics: Adult; Brain Neoplasms; Humans; Hydrocephalus; Pineal Gland; Pinealoma; Ventriculostomy
PubMed: 34999267
DOI: 10.1016/j.wneu.2022.01.005 -
Folia Neuropathologica 2023BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain...
BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain tumours investigated. Immunohistochemical detection of BCOR expression may therefore serve as a potential diagnostic marker. Nevertheless, in rare paediatric glioma cases recurrent EP300-BCOR fusions were detected, which resulted in strong BCOR immunopositivity. We have therefore examined other, not analysed so far, types of central nervous system (CNS) tumours, pineoblastoma and germinoma, to assess a potential involvement of BCOR in these tumours. Levels of BCOR RNA expression were investigated by NanoString nCounter system analysis in a series of altogether 66 high grade paediatric tumours, including four pineoblastoma cases. Immunohistological detection of BCOR was performed in eight pineoblastoma, five germinoma and four atypical teratoid rhabdoid tumours (ATRTs), all located in the pineal region. We detected BCOR expression in all pineoblastomas, at the RNA and protein levels, but not in germinomas and ATRTs. Further analysis of pineoblastoma samples did not reveal the presence of either BCOR internal tandem duplication or BCOR fusion involvement. Positive immunohistological BCOR nuclear reaction in pineoblastoma may therefore differentiate this type of tumour from other high grade tumours located in the pineal region.
Topics: Humans; Child; Pinealoma; Brain Neoplasms; Germinoma; RNA; Rhabdoid Tumor; Pineal Gland; Proto-Oncogene Proteins; Repressor Proteins
PubMed: 37587886
DOI: 10.5114/fn.2023.129377 -
Indian Journal of Pathology &... 2023Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and...
Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy.
Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis after subtotal tumor resection and adjuvant radiotherapy. This case was a 58-year-old male with an unsteady gait for 2 months. Enhanced brain magnetic resonance imaging revealed a heterogeneous mass involving the pineal region. The initial pathological diagnosis of pineocytoma was confirmed after subtotal tumor resection. Two years after adjuvant radiotherapy to the primary site, the magnetic resonance imaging showed C2 and T2 metastatic lesions, with the final pathological diagnosis being pineal parenchymal tumor (PPT) with intermediate differentiation after the removal of T2 intramedullary tumor. After that adjuvant radiotherapy at the cervical and thoracic spinal cord was completed. There was no recurrence of the tumor 1 year after the radiotherapy. We report a rare case of pineocytoma with malignant transformation to PPT with intermediate differentiation and leptomeningeal dissemination.
Topics: Male; Humans; Middle Aged; Pinealoma; Brain Neoplasms; Radiotherapy, Adjuvant; Pineal Gland; Spinal Cord; Cell Transformation, Neoplastic
PubMed: 36656225
DOI: 10.4103/ijpm.ijpm_817_21 -
Digital Journal of Ophthalmology : DJO Jun 2021
Topics: Adult; Humans; Magnetic Resonance Imaging; Male; Neoplasms, Germ Cell and Embryonal; Nystagmus, Pathologic; Pinealoma; Pituitary Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Visual Fields
PubMed: 34512208
DOI: 10.5693/djo.02.2020.12.002