scholarly journals PATH-32. CLINICAL AND MUTATIONAL PROFILES OF ADULT MEDULLOBLASTOMA GROUPS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii171-ii171
Author(s):  
Gabriel Chun-Hei Wong ◽  
Queenie Junqi Huang ◽  
Manix Fung Man Poon ◽  
Nellie Yuk-Fei Chung ◽  
Queenie Hoi-Wing Wong ◽  
...  
Keyword(s):  
Significant Proportion ◽  
Large Cell ◽  
Prognostic Impact ◽  
Adult Group ◽  
Tp53 Mutations ◽  
Adult Medulloblastoma ◽  
Group 4 ◽  
Tert Promoter ◽  
Recurrent Mutations ◽  
Group 3

Abstract INTRODUCTION Adult medulloblastomas are clinically and molecularly understudied due to their rarity. METHODS We studied a cohort of 101 adult medulloblastomas grouped by Nanostring assay. We performed targeted sequencing on exonic regions of 69 genes implicated in medulloblastoma, and Sanger sequencing for TERT promoter hotspot mutations. RESULTS Median age was 27 (range 19-63), and 9.5% were metastatic at diagnosis. SHH accounted for 50% of cases. Unlike previous studies, Group 3 comprised a significant proportion (14%) of adult medulloblastomas, comparable to WNT (19%) and Group 4 (18%). Median follow-up was 51.1 months. Median OS and PFS were 102 and 99 months respectively. In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in adults, for both OS (p=0.956) and PFS (p=0.162). Most frequently mutated genes were TERT (including promoter, mutated in 35% cases), chromatin modifiers KMT2C (32%) and KMT2D (31%), TCF4 (31%), PTCH1 (26%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. 5 WNT cases harboured concurrent CTNNB1 and PTCH1 mutations. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and seldom downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 71% of adult SHH patients, and were restricted to this group. Adult Group 3 patients lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 patients had recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%) in adult medulloblastomas. CONCLUSIONS We identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their treatment and risk stratification. Importantly, molecular groups were not prognostic in adult medulloblastoma, TP53 mutations were enriched in adult WNT, and MYC amplifications were absent in adult Group 3.

scholarly journals Clinical and mutational profiles of adult medulloblastoma groups

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Gabriel Chun-Hei Wong ◽  
Kay Ka-Wai Li ◽  
Wei-Wei Wang ◽  
Anthony Pak-Yin Liu ◽  
Queenie Junqi Huang ◽  
...  
Keyword(s):  
Large Cell ◽  
Prognostic Impact ◽  
Adult Group ◽  
Adult Medulloblastoma ◽  
Group 4 ◽  
Tert Promoter ◽  
Mutational Status ◽  
Recurrent Mutations ◽  
Group 3 ◽  
Promoter Mutations

Abstract Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.

scholarly journals MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii388-iii389
Author(s):  
Martin Mynarek ◽  
Katja von Hoff ◽  
Torsten Pietsch ◽  
Holger Ottensmeier ◽  
Monika Warmuth-Metz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Systemic Chemotherapy ◽  
Validation Cohort ◽  
Large Cell ◽  
Prognostic Impact ◽  
Free Survival ◽  
Group 4 ◽  
Dna Methylation Profiling ◽  
Group 3 ◽  
Methylation Profiling

Abstract OBJECTIVE To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy. PATIENTS AND METHODS Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71). RESULTS Patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) (n=42) had 93% 5-year PFS, 100% 5-year OS and 93% 5-year CSI-free survival. Patients with CMB/LCA (n=45) had 37% 5y-PFS, 62% 5y-OS and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in CMB/LCA patients. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH_INF subgroup. Group 3 patients (5y-PFS 36% [n=14]) relapsed more frequently than SHH_INF (5y-PFS 93% [n=28]) or Group 4 patients (5y-PFS 83% [n=6], p<0.001). SHH_INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I 73% vs. iSHH-II 83%, p=0.25, n=99). Mean IQ was 90 (radiotherapy-free survivors) vs. 74 (patients that received CSI) [p=0.012]. CONCLUSION Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH-subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in non-WNT/non-SHH CMB/LCA patients was not improved by local radiotherapy. Survival was more favorable in patients with Group 4 than in patients with Group 3 medulloblastoma.

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

2020 ◽  
Vol 38 (18) ◽  
pp. 2028-2040 ◽  
Author(s):  
Martin Mynarek ◽  
Katja von Hoff ◽  
Torsten Pietsch ◽  
Holger Ottensmeier ◽  
Monika Warmuth-Metz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Systemic Chemotherapy ◽  
Validation Cohort ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Large Cell ◽  
Prognostic Impact ◽  
Free Survival ◽  
Group 4 ◽  
Group 3

PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia. RESULTS Five years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012). CONCLUSION Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.

scholarly journals SEOM clinical guideline for management of adult medulloblastoma (2020)

2021 ◽  
Author(s):  
R. Luque ◽  
M. Benavides ◽  
S. del Barco ◽  
L. Egaña ◽  
J. García-Gómez ◽  
...  
Keyword(s):  
Residual Tumor ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Molecular Alterations ◽  
Adult Medulloblastoma ◽  
Group 4 ◽  
Risk Patients ◽  
Standard Risk

AbstractRecent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Clinical Characteristic and Molecular Subgroups of Thai Pediatric Medulloblastomas at Queen Sirikit National Institute of Child Health

2021 ◽  
Vol 104 (10) ◽  
pp. 1648-1657
Keyword(s):  
Child Health ◽  
Signaling Pathway ◽  
Survival Rates ◽  
Large Cell ◽  
Disease Classification ◽  
Molecular Subgroups ◽  
Molecular Subgroup ◽  
Group 4 ◽  
Group 3 ◽  
Clinical Records

Objective: To determine the correlation between clinical characteristics and molecular subgroups of medulloblastoma (MB) in Thai pediatric patients at the Queen Sirikit National Institute of Child Health (QSNICH), Thailand. Materials and Methods: MB specimens operated between 2004 and 2018 were classified by Nanostring into four molecular subgroups, including Wingless signaling pathway (WNT), Sonic Hedgehog signaling pathway (SHH), Group 3, and Group 4. For the present cases, the clinical records were retrospectively analyzed. Results: Twenty-two MB cases with complete clinical records were analyzed. Group 4 was the most common molecular subgroup (31.82%), followed by WNT (27.27%), SHH (22.73%), and Group 3 (18.18%). The histologic subtypes included 18, three, and one cases of classic MB, MB with extensive nodularity (MBEN), and large cell MB, respectively. All SHH MBs were found in infants. All MBENs belonged to SHH subgroup, and the large cell MB was Group 3. All six WNT MB cases did not experience tumor recurrence. Five-year cause specific survival rates were 100% in WNT, 60% in SHH, 57.1% in Group 4, and 0% in Group 3. Five-year recurrence-free survival rates were 100% in WNT, 42.9% in Group 4, and 0% in SHH and Group 3. Conclusion: MB is a heterogeneous disease. Classification of MB, especially at the molecular subtype, is helpful for the management and prognostication. Keywords: Medulloblastoma; Molecular subgroup

scholarly journals MBRS-61. MOLECULAR SUB-GROUPING OF PEDIATRIC MEDULLOBLASTOMA: CORRELATION WITH CLINICAL AND HISTOLOGICAL FEATURES, A SINGLE INSTITUTIONAL STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii408-iii408
Author(s):  
Gauri Deshpande ◽  
Mamta Gurav ◽  
Omshree Shetty ◽  
Vinayak Kadam ◽  
Vishal Chaubey ◽  
...  
Keyword(s):  
P53 Protein ◽  
Age Groups ◽  
Large Cell ◽  
Protein Coding ◽  
Real Time Quantitative Pcr ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3 ◽  
Protein Immunoreactivity

Abstract INTRODUCTION Molecular subgroups of pediatric medulloblastomas are distinctive in infantile and non-infantile age-groups. METHODS Real-time quantitative PCR based GEP of customized 12 protein-coding genes was performed on 206 FFPE childhood medulloblastoma samples. FISH for MYC amplification, monosomy 6 and sequencing for CTNNB1 exon 3 mutation were done in relevant cases. H&E and reticulin-stained slides were used for histological subtyping. p53-protein immunoreactivity pattern was noted. RESULTS Infantile (n=33) comprised 57.6% SHH-activated (desmoplastic: 73.7%; MBEN: 15.8% and classic: 10.5%), 21.2% group 3 (large cell/anaplastic [LCA]: 28.6% and none were desmoplastic) and 12% group 4. 40% of group 3 patients died of disease and 21% of the SHH-activated (all desmoplastic) had subsequent local recurrence. Non-infantile (n=173) comprised 19.4% WNT-activated, 12.9% SHH-activated (15% classic, 30% desmoplastic, 10% paucinodular), 19.4% group 3 (63.3% classic & 26.7% LCA), 48.4% group 4 (73.3% classic, 5.3% desmoplastic, 10.7% paucinodular & 1.4% LCA), and non-WNT/non-SHH (NWNS), NOS (n=14,9%) and unclassified (n=4,2.6%). None of WNT-activated were desmoplastic/LCA histology. Non-infantile WNT-activated and group 3 MBs showed 90% monosomy 6 & CTNNB1 mutation, and 16.7% MYC-amplification respectively. 17.4% (13% spinal, 4.4% local) WNT-activated, 31% (12.5% local, 18.5% distant [spinal: 12.5%, intracranial:6%]) SHH-activated, 27% (18% both spinal and local, 9% spinal) group 3 and 31.5% (7.4% local, 5.5% intracranial, 11.2% spinal, 7.4% both spinal and local) group 4 showed metastases during follow up. CONCLUSIONS SHH-activated and group 3 are the common infantile subgroups but group 4 is not non-existent in infantile age. No desmoplastic (including paucinodular) histological subtype is of WNT- activated and group 3.

scholarly journals Do MYC Alterations Matter in HIV-Associated Large B Cell Lymphomas? the "Euromyc" Study (a European retrospective study)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2506-2506
Author(s):  
Chiara Pagani ◽  
Chiara Rusconi ◽  
Alessia Dalla Pria ◽  
Emanuele Ravano ◽  
Philipp Schommers ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Clinical Characteristics ◽  
Prognostic Impact ◽  
Advisory Committees ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Large B Cell ◽  
Group 1

Abstract Introduction: In the general HIV negative population, patients (pts) with diffuse large B cell lymphoma (DLBCL) or high grade B cell lymphoma (HGBCL) carrying MYC rearrangements and BCL2 and/or BCL-6 translocations [double hit (DHL) or triple hit lymphomas (THL)] have shown a dismal prognosis when treated with standard R-CHOP and are frequently candidates to intensive therapeutic regimens, without having a standard of care. Moreover, several authors have demonstrated a negative prognostic impact of isolated MYC rearrangements [single hit lymphomas (SHL)] and the best therapeutic approach for SHL are even less clear. In HIV-associated "non Burkitt" large B cell lymphomas (Ly), scanty data are available on the prevalence and the clinical and prognostic impact of MYC rearrangements, with or without BCL2 and BCL6 concomitant translocations. Due to the peculiar biology and pathogenesis of HIV-associated Ly, data from HIV negative population cannot be simply translated to the HIV positive pts. Aim: To evaluate the impact of MYC rearrangements or translocations (isolated or with BCL2 and/or BCL6 translocations) on clinical features and outcome of HIV-associated large B cell Ly. Methods: Retrospective analysis of clinical characteristics, treatment received and outcome of all HIV-associated large B cell Ly [including DLBCL, B cell Ly unclassifiable, with features intermediate between DLBCL and Burkitt (BCLU), and HGBL] with MYC rearrangements or translocations, evaluated by FISH analysis, in 11 European centers, and comparison with pts who do not have the MYC alterations. Results: One hundred-sixty-one pts were enrolled, 49 (30%) had MYC translocation or other MYC rearrangements (MYC+ pts), and 112 (70%) were negative for MYC mutation (7 pts had MYC increased copy number) (MYC- pts). Table 1 shows the clinical characteristics of the two groups, and the treatment received. MYC+ pts had higher involvement of central nervous system at presentation (17% vs 3%, p 0,023), higher Ki67% (median 91% vs 85%, p 0,005), histology other than DLBCL (32% vs 9%, p 0,0001), concomitant translocation of BCL2 (14% vs 3%, p 0,022), germinal center B phenotype (according to Hans algorithm) (85% vs 49%, p 0,0001). No differences in CD4 count or HIV viral load at Ly diagnosis were found, while a previous diagnosis of AIDS was more frequent in the MYC- group (27% vs 10%, p 0,023). MYC+ pts received more frequently intensive treatment (iCT) (41% vs 12%, p 0,0001) and less frequently the standard CHOP regimen (41% vs 74%, p 0,001). Ten pts (9%) had a DHL/THL and had similar clinical characteristics compared to SHL. With a median follow-up of 62 months, there were no significant differences in overall survival (OS) and progression-free survival (PFS) between MYC+ and MYC- pts (5 years-OS and PFS were respectively 55% and 47% in MYC+ and 59% and 53% in MYC- pts). In univariate analysis for the whole population, IPI≥3, ECOG≥ 2 and increased LDH were related to a worse OS and PFS while BCL2 translocation correlated with shorter PFS alone. In multivariate analysis ECOG and IPI mainteined their negative prognostic impact on OS and PFS. In the MYC+ group, 41% pts received R-CHOP or CHOP-like treatment (group 1), 16% infusional therapy (group 2), 41% iCT (group 3), 2% palliative therapy (PT) (group 4); 5-years OS and PFS were 47% and 32% for group 1, 47% and 37% for group 2, 67% and 68% for group 3 and both 0% for group 4. Median OS and PFS were respectively 18 and 2 months for group 1, 29 and 7 months for group 2, both not reached for group 3, both 2 months for group 4. A significant difference between group 3 and group 1 both in therm of OS (p 0,054) and PFS (p 0,005) was observed (Figure 1). Pts with DHL/THL received R-CHOP (40%), infusional schedule (30%), iCT (20%) and PT (10%). No significant difference in term of PFS and OS were observed for each treatment group with DHL/THL respect to those with SHL. In DHL/THL, 5 years OS and PFS were 50% and 30%, respectively; in SHL 56% and 51%, respectively. Of note, no pts treated with iCT died from toxicity in the MYC+ group. Conclusion: In this retrospective analysis, MYC+ pts had not different clinical characteristics compared to MYC- pts other than higher proliferative index and and more CNS involvement at diagnosis. MYC+ pts were frequently treated with iCT, this aggressive approach seemed feasible and could allow to obtain better outcome compared to standard R-CHOP treatment but further prospective studies are needed. Figure 1 Figure 1. Disclosures Bastos-Oreiro: F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau. Rossi: Novartis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

scholarly journals 4. “Biphasic” histology is associated with the non-WNT/SHH molecular subtype of medulloblastoma

2015 ◽  
Vol 42 (S2) ◽  
pp. S2-S3
Author(s):  
C. Dunham ◽  
C. Foster ◽  
J. Triscott ◽  
S. Dunn
Keyword(s):  
Random Distribution ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Large Cell ◽  
Chromosome 17 ◽  
Histologic Subtype ◽  
Group 4 ◽  
Glass Slides ◽  
Group 3 ◽  
Analysis System

IntroductionIn 2007, Ellison et al coined the term “biphasic” medulloblastoma (B-MB) to characterize histology that mimicked the desmoplastic nodular (DN) variant on routine staining, but which lacked internodular reticulin deposition. Via interphase FISH, and utilizing markers for 9q22 and chromosome 17 alterations (ie, -17p and i17q), Ellison et al. suggested that B-MB and DN-MB were genetically different.MethodsWe performed a clinicopathologic review of MBs treated at BCCH from 1986-2011. Using nanoString’s n Counter Analysis System (nCAS), each tumor was molecularly subtyped (ie, WNT, SHH, group 3 or group 4). All original glass slides were reviewed to determine WHO histologic subtype [ie, classic, large cell anaplastic (LCA), DN, MB with extensive nodularity (MBEN)]. Tumors were also evaluated for nodularity (scattered vs. frequent) and advanced neuronal differentiation. Reticulin staining was assessed on all cases.Results20 B-MB were identified; by WHO definition, most of these resided within the classic category (N=19), while one was LCA. 13 of 20 B-MB displayed ‘scattered” nodules; by molecular subtype, these included eight group 4, four group 3 and one WNT tumors. Seven of the 20 B-MB exhibited “frequent” nodules; by molecular subtype, these included six group 4 and one group 3 tumors. Statistical analysis confirmed this non random distribution of B-MB across molecular subtypes.ConclusionOur data confirm the work of Ellison et al. that suggested B-MB is genetically different than DN-MB. In particular, B-MB resides in the non-WNT/SHH molecular category, but especially amongst group 4 when nodularity is “frequent”.

scholarly journals LINC-15. OUTCOME OF CHINESE CHILDREN WITH MEDULLOBLASTOMA: A MULTI-CENTER EXPERIENCE WITH RISK-ADAPTED THERAPY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii381-iii381
Author(s):  
Xiaofei Sun ◽  
Anthony Pak-Yin Liu ◽  
Qunying Yang ◽  
Jian Wang ◽  
Shaoxiong Wu ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Tumor ◽  
Large Cell ◽  
High Dose ◽  
Average Risk ◽  
Group 4 ◽  
High Risk Disease ◽  
Significant Difference ◽  
Oncology Care ◽  
Group 3

Abstract BACKGROUND Medulloblastoma is the commonest brain tumor in young children but literature on Chinese is scarce. We hereby present the outcome of children with medulloblastoma managed according to a risk- and age-stratified guideline from ten institutions across China. METHODS Patients &lt;18 years of age diagnosed with medulloblastoma between January 2016 and April 2019 were reviewed. Patients ≥3 years, stratified into average-risk (≤1.5cm2 residual tumor, non-metastatic, non-anaplastic histology) and high-risk (others) groups, were treated with risk-adapted craniospinal irradiation (average-risk: 23.4Gy, high-risk: 36Gy), tumor boost, and chemotherapy (lomustine/cisplatin/vincristine). Patients &lt;3 years (considered high-risk, other than patients with localized and desmoplastic/nodular histology) received chemotherapy (cyclophosphamide/vincristine, high-dose methotrexate, carboplatin/etoposide) with/without delayed irradiation. RESULTS 112 patients were included with a median age at diagnosis of 6.5 years (range: 0.5–16.7). 16 patients (14.3%) had residual tumor &gt;1.5cm2 and 36 (32%) had metastasis. Available data on histological subtype (n=87) were classic in 56 (64%), desmoplastic/nodular or extensive nodularity in 23 (26%), and large cell/anaplastic in 8 (9%). Molecular subgrouping (n=55) assigned tumors as WNT-activated (n=8, 15%), SHH-activated (n=17, 31%), Group 3 (n=12, 22%) and Group 4 (n=18, 33%). Respective 2-year EFS/OS for patients ≥3 and &lt;3 years were 86.0±4.0%/96.4±2.1% and 57.8±12.6%/81.4±9.8% (EFS/OS p&lt;0.001/p=0.009). Significant difference in outcome was also observed between patients with average-risk and high-risk disease (EFS/OS p=0.006/p=0.018). CONCLUSION We demonstrated feasibility in protocolizing the inter-disciplinary treatment for medulloblastoma in China. This will serve as a prototype for the standardization of pediatric neuro-oncology care in the country.

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

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