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European Journal of Radiology Feb 2023To evaluate the effectiveness of diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) for differentiation between germinoma and other pineal region...
PURPOSE
To evaluate the effectiveness of diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) for differentiation between germinoma and other pineal region tumors.
METHOD
This retrospective study consisted of 72 patients with pathologically proven pineal region tumors between January 2010 and August 2020. Tumors were classified as germinomas (40), non-germinomatous germ cell tumors (11) (NGGCT), pineal parenchymal tumors (10) (PPT), and other types of tumors (11). Visual scale score, ADC values and SWI intratumoral susceptibility signal (ITSS) score were analyzed and compared to histopathology data.
RESULTS
The mean apparent diffusion coefficient (ADCmean) and minimum apparent diffusion coefficient (ADCmin) ratio of germinoma were significantly lower than NGGCT. ADCmean or ADCmin cut-off ratio of ≤ 1.48 or ≤ 1.32 allowed for discrimination between germinoma and NGGCT with sensitivity and specificity of 100 % and 63.6 %. An ADCmin cut-off ratio of ≥ 0.93 allowed for discrimination between germinoma and PPT with sensitivity and specificity of 60 % and 80.0 %. ADCmin cut-off ratio of ≤ 1.15 allowed for discrimination of germinoma from other types of tumors with sensitivity and specificity of 87.5 % and 54.5 %.
CONCLUSIONS
ADC ratio can differentiate germinoma from other types of pineal region tumors. Our initial results suggest that ITSS score was not significantly correlated with specific histology subtype.
Topics: Humans; Pinealoma; Retrospective Studies; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Germinoma; Neoplasms, Germ Cell and Embryonal; Cell Differentiation; Brain Neoplasms; Pineal Gland
PubMed: 36584565
DOI: 10.1016/j.ejrad.2022.110663 -
Neuro-oncology Practice Aug 2023alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary...
BACKGROUND
alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary -associated CNS sarcoma" (DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy.
METHODS
We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed.
RESULTS
Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic variants were present in two patients, 75% of cases had more than one somatic alteration in , and the most frequent commutation was . Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in and . Overall survival was 30.8 months.
CONCLUSIONS
DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in , , and and most alterations at progression were related to , and signaling pathways.
PubMed: 37457227
DOI: 10.1093/nop/npad014 -
Neurology India 2019Pineal gland tumors range from the well-differentiated "pineocytoma" [World Health Organization (WHO) grade I], which have a very good prognosis, to the aggressive and...
BACKGROUND
Pineal gland tumors range from the well-differentiated "pineocytoma" [World Health Organization (WHO) grade I], which have a very good prognosis, to the aggressive and poorly differentiated "pineoblastoma" (WHO grade IV) with "pineal parenchymal tumor of intermediate differentiation" (PPTID; WHO grades II and III) occupying intermediary differentiation and prognosis. Papillary tumor of the pineal region (PTPR; WHO grades II and III) is a distinct entity with propensity for recurrence and spinal dissemination. However, the diagnostic criteria to differentiate these entities, especially between WHO grades II and III of both PPTID and PTPR, remain nebulous.
OBJECTIVE
To evaluate the relative frequency of the individual entities and histomorphological (including the proliferation indices) features across the spectrum of pineal parenchymal tumors (PPTs) [including PTPRs] along their course.
DESIGN
All cases of PPTs were retrieved, reviewed, and graded based on the histological criteria defined in the literature.
RESULTS
PPTID, more commonly seen in young adults, was the most common subtype of PPT. This was followed by pineoblastoma which was more commonly seen in children. Clinical progression was seen in both grades II and III of PPTID; however, it was more commonly seen in cases with a MIB1 labeling index of >10%. PTPRs (both grades II and III) showed an aggressive histological transformation and also intraparenchymal metastasis.
CONCLUSION
PPTIDs are the most common adult primary PPTs and have the potential to progress and disseminate in both grades II and III. Both grades of PTPRs have a metastatic potential. These findings suggest the need for postoperative adjuvant therapy in both grades of PPTID and PTPR.
Topics: Brain Neoplasms; Child; Combined Modality Therapy; Female; Humans; Male; Neoplasm Recurrence, Local; Pineal Gland; Pinealoma; Prognosis; Young Adult
PubMed: 31085866
DOI: 10.4103/0028-3886.258045 -
BioRxiv : the Preprint Server For... May 2024Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function . As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase...
Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function . As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma (MB) , the most common embryonal brain tumor in children, and pineoblastoma . These mutations impart gain-of-function to KBTBD4 to induce aberrant degradation of the transcriptional corepressor CoREST . However, their mechanism of action remains unresolved. Here, we elucidate the mechanistic basis by which KBTBD4 mutations promote CoREST degradation through engaging HDAC1/2, the direct neomorphic target of the substrate receptor. Using deep mutational scanning, we systematically map the mutational landscape of the KBTBD4 cancer hotspot, revealing distinct preferences by which insertions and substitutions can promote gain-of-function and the critical residues involved in the hotspot interaction. Cryo-electron microscopy (cryo-EM) analysis of two distinct KBTBD4 cancer mutants bound to LSD1-HDAC1-CoREST reveals that a KBTBD4 homodimer asymmetrically engages HDAC1 with two KELCH-repeat propeller domains. The interface between HDAC1 and one of the KBTBD4 propellers is stabilized by the MB mutations, which directly insert a bulky side chain into the active site pocket of HDAC1. Our structural and mutational analyses inform how this hotspot E3-neo-substrate interface can be chemically modulated. First, our results unveil a converging shape complementarity-based mechanism between gain-of-function E3 mutations and a molecular glue degrader, UM171. Second, we demonstrate that HDAC1/2 inhibitors can block the mutant KBTBD4-HDAC1 interface, the aberrant degradation of CoREST, and the growth of KBTBD4-mutant MB models. Altogether, our work reveals the structural and mechanistic basis of cancer mutation-driven neomorphic protein-protein interactions and pharmacological strategies to modulate their action for therapeutic applications.
PubMed: 38798357
DOI: 10.1101/2024.05.14.593970 -
Acta Neuropathologica Oct 2014Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1...
Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1 mutation in a child with a PinB. This was accompanied by loss of heterozygosity (LOH) of the wild-type allele within the tumour. We set out to establish the prevalence of DICER1 mutations in an opportunistically ascertained series of PinBs. Twenty-one PinB cases were studied: Eighteen cases had not undergone previous testing for DICER1 mutations; three patients were known carriers of germ-line DICER1 mutations. The eighteen PinBs were sequenced by Sanger and/or Fluidigm-based next-generation sequencing to identify DICER1 mutations in blood gDNA and/or tumour gDNA. Testing for somatic DICER1 mutations was also conducted on one case with a known germ-line DICER1 mutation. From the eighteen PinBs, we identified four deleterious DICER1 mutations, three of which were germ line in origin, and one for which a germ line versus somatic origin could not be determined; in all four, the second allele was also inactivated leading to complete loss of DICER1 protein. No somatic DICER1 RNase IIIb mutations were identified. One PinB arising in a germ-line DICER1 mutation carrier was found to have LOH. This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility gene for PinB and demonstrates PinB to be a manifestation of a germ-line DICER1 mutation. The means by which the second allele is inactivated may differ from other DICER1-related tumours.
Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; DEAD-box RNA Helicases; DNA Mutational Analysis; Family Health; Female; Germ-Line Mutation; Humans; Infant; Male; Pineal Gland; Pinealoma; Ribonuclease III; Young Adult
PubMed: 25022261
DOI: 10.1007/s00401-014-1318-7 -
Surgical Neurology International 2022In recent years, the efficacy of 5-aminolevulinic acid photodynamic diagnosis (5-ALA PDD) has been reported for various types of brain tumors, including malignant...
BACKGROUND
In recent years, the efficacy of 5-aminolevulinic acid photodynamic diagnosis (5-ALA PDD) has been reported for various types of brain tumors, including malignant glioma. In addition, many reports have been published on the usefulness of neuroendoscopic surgery for intraventricular lesions. However, no systematic report is available on the combined use of 5-ALA PDD and neuroendoscopy for various intraventricular tumors.
METHODS
We report 17 consecutive patients with intraventricular tumors. All patients received oral 5-ALA preoperatively and underwent endoscopic surgical treatment (resection or biopsy). We use a rigid endoscope with a built-in PDD system for intraoperative observation.
RESULTS
Seven resections and 10 biopsies were performed. Histopathological diagnosis was confirmed in all 17 cases. Gross total resection was achieved in six of seven cases. The fluorescence positivity rates for each tumor were glioblastoma 100% (2/2), low-grade glioma 67% (2/3), subependymoma 0% (0/1), medulloblastoma 100% (1/1), pineoblastoma 0% (0/1), germ cell tumor 75% (3/4), diffuse large B-cell lymphoma 33% (1/3), and metastatic tumor 100% (2/2).
CONCLUSION
Our method has the potential to improve detection of residual tumors in blind spots and deep areas, as well as the accuracy and safety of biopsy procedures for intraventricular lesions that are difficult to view and treat under a microscope.
PubMed: 35928327
DOI: 10.25259/SNI_488_2022 -
Ophthalmic Genetics Mar 1997The aim of this survey was to review the different studies regarding the occurrence of second primary tumours (SPT) among survivors of retinoblastoma. (Review)
Review
PURPOSE
The aim of this survey was to review the different studies regarding the occurrence of second primary tumours (SPT) among survivors of retinoblastoma.
METHODS
Ovid (Medline, Current contents life, Psychlit, Embase) was searched for the years 1966-1995 using the mesh headings: 'retinoblastoma', 'second primary neoplasms', and 'multiple primary neoplasms'. The inclusion criteria were: the study should involve 50 patients or more and should not be limited to one specific SPT. A checklist with criteria regarding the study design and the results was applied to each study.
RESULTS
Eleven studies were identified which met the inclusion criteria. Thirty-five different types of SPT (Ntotal = 243) were reported. Most of them were osteosarcomas (37.0%), followed by melanomas (7.4%), soft-tissue sarcomas (6.9%), brain tumors (4.5%), fibrosarcomas (3.3%), chondrosarcomas (3.3%), and sarcomas (3.3%). Less frequently reported were leukemias (2:4%), sebaceous cell carcinomas (1.6%), and non-Hodgkin lymphomas (1.6%). Pineoblastoma, which in fact is a trilateral retinoblastoma and not an SPT, was found in 2.4%. Despite the differences, all 11 studies showed a higher incidence of SPT compared to the general population. Only 4 studies were judged to be free from selection bias, reporting a cumulative incidence of SPT of 8.4% 18 years after diagnosis, 15.7% at the age of 20 years, 19% at the age of 35 years, and a relative risk of 15.4 for SPT, respectively.
CONCLUSION
SPT is a serious problem for the survivors of hereditary retinoblastoma and its importance should be recognized in (genetic) counseling of patients.
Topics: Adolescent; Adult; Bone Neoplasms; Brain Neoplasms; Child; Child, Preschool; Eye Neoplasms; Follow-Up Studies; Humans; Incidence; Infant; Melanoma; Neoplasms, Second Primary; Pineal Gland; Pinealoma; Retinoblastoma; Retrospective Studies; Risk Factors; Sarcoma; Soft Tissue Neoplasms; Survival Rate
PubMed: 9134547
DOI: 10.3109/13816819709057880 -
Acta Neuropathologica Dec 2023
Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics.
Topics: Humans; Pinealoma; Pineal Gland; Brain Neoplasms
PubMed: 37776353
DOI: 10.1007/s00401-023-02638-1 -
Case Reports in Oncological Medicine 2014Pineoblastomas are rare, malignant, pineal region lesions that account for <0.1% of all intracranial tumors and can metastasize along the neuroaxis. Pineoblastomas are...
Pineoblastomas are rare, malignant, pineal region lesions that account for <0.1% of all intracranial tumors and can metastasize along the neuroaxis. Pineoblastomas are more common in children than in adults and adults account for <10% of patients. The management of pinealoblastoma is multimodality approach, surgery followed with radiation and chemotherapy. In view of aggressive nature few centres use high dose chemotherapy with autologus stem cell transplant in newly diagnosed cases but in recurrent setting the literature is very sparse. The present case represents the management of pinealoblastoma in the recurrent setting with reirradiation and adjuvant carmustine chemotherapy wherein the management guidelines are not definitive.
PubMed: 25210636
DOI: 10.1155/2014/135435