Desmoplastic/nodular Medulloblastoma Research Articles

Molecular Subgrouping Based on Immunohistochemistry in Medulloblastoma: a Single-Center Experience.

Medulloblastomas (MBs) are the most commonly observed malignant brain tumors affecting children; they can be classified into molecular subgroups based on the 2016 and 2021 WHO classifications, as WNT-activated, SHH-activated and TP53-wild type, SHH-activated and TP53-mutant, and non-WNT/non-SHH. However, the molecular methods to determine these subgroups are not easily accessible for routine testing as they are expensive. Here, we investigated the efficacy of immunohistochemical methods to determine molecular subgroups and prognostic predictions of MB. β-catenin, GAB1, YAP1, filamin A and p53 were immunohistochemically stained, and MYC and MYCN fluorescent in situ hybridization (FISH) procedures were applied to 218 cases in our series. Based on the histomorphological characteristics of the cases, 67.9% were deemed classic MB; 15.6% as desmoplastic/nodular medulloblastoma (DNMB); 12.8% as large cell/anaplastic (LC/A) MB; 3.7% as medulloblastoma with extensive nodularity (MBEN). Molecular characteristics revealed that 50.5% had non-WNT/non-SHH; 33.9% had SHH-activated and TP53-wildtype; 8.7% had WNT-activated; 6.9% had SHH-activated and TP53-mutant. According to the survival curves, LC/A MBs or non-WNT/non-SHH tumors showed the worst prognosis, whereas DNMBs and WNT-activated tumors showed the best prognosis. Classic MBs or SHH-activated tumors showed a moderate course. MYCN amplification was found to act as an independent poor prognostic factor in the study. The distribution of histological subtypes and molecular subgroups, amplification rates, and prognostic data obtained through immunohistochemical methods in our study were consistent with those reported in the literature. It was therefore hypothesized that the determination of molecular subgroups by immunohistochemical methods can be useful in daily diagnostic practice, especially in centers with limited access to molecular techniques.

Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than 2 subgroups.

The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse. One hundred and forty-four patients with DMB (n = 99) or MBEN (n = 45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients were evaluated. Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs. 93% [MBEN]). Patients aged >3 years were associated with more unfavorable 5y-PFS (47% [>3 years] vs. 85% [<1 year] vs. 84% [1-3 years]). DNA methylation profiles available (n = 78) were reclassified according to the 2021 WHO classification into SHH-1 (n = 39), SHH-2 (n = 38), and SHH-3 (n = 1). Hierarchical clustering delineated 2 subgroups among SHH-2: SHH-2a (n = 19) and SHH-2b (n = 19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs. 83% [SHH-1] vs. 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using 2 independent cohorts (total n = 188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations. These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with a higher risk of relapse.

Survival Study in Pediatric Patients with Medulloblastoma in a General Hospital in Tehran, Iran

Abstract Brain tumours are the most common solid tumours that afflict the pediatric population. Me-dulloblastoma (MB) is the most common malignant brain tumour in children, constituting nearly 20% of all pediatric brain tumours. This study is an evaluation of overall survival rate of pediatric MB tumour patients after one year, three years, five years, and ten years according to case studies. From 22 June 2009 to 19 December 2019, a total of 22 patients ranging in age from 1 to 14 years old underwent tumour removal. These patients were followed to determine survival rate. Tumours were classified into three pathological subtypes: The first was classic MB, the second was desmoplastic nodular MB and MB with extensive nodularity, and the third was large cell and anaplastic MB. Patients who were 3 years old or older had a better survival rate than younger patients (log-rank test; p = 0.01). The survival probability in the older children group (55%) was significant compared to the group of younger children (29%). The Kaplan–Meier survival curves of the patients were significantly different. The ten-year survival rates in the average- and high-risk groups were 64.4% and 86.0%, respectively. After a follow-up of 120 months (median range = 60 months), recurrence or progression was observed in 22 patients and 15 patients were still alive. The estimated 10-year overall survival rates for all patients were 49.36 ± 38.33. MB patients’ survival rate was quite good in our hospital. More than half of the patients, most of whom had large cell anaplastic and classic type MB, survived the 10-year follow-up period without any problems.

MBCL-27. ASSOCIATION OF MEDULLOBLASTOMA WITH CHARCOT-MARIE-TOOTH DISEASE

Charcot-Marie-Tooth disease (CMT) is one of the most common hereditary neurological disorders and damages peripheral nerves that results in motor and sensory disturbance. Association of medulloblastoma (MBL) with CMT has been rarely reported. A one-year-old male was referred to our hospital because of cerebellar mass. He had partial resection of the tumor, and was pathologically diagnosed as having desmoplastic nodular medulloblastoma. He received chemotherapy according to the HIT protocol, however, developed severe peripheral neurotoxicity in the initial stage of the treatment. Reinvestigation of family history revealed his mother, grandmother, and aunt had muscle weakness. We suspected he had an inherited neurological disease including CMT, and discontinued administration of vincristine. Fluorescence in situ hybridization analysis detected duplication of PMP22 gene located on 17p11.2, confirming the diagnosis of CMT1A. He completed the rest of chemotherapy without vincristine, and remained in complete remission for four years from the end of treatment. In the literature, there are reports of patients with CMT who developed MBL and were complicated with severe peripheral neurotoxicity due to the use of vincristine. The present case, along with previous reports, suggests that medulloblastoma can develop in patients with CMT and reminds the importance of recalling the possibility of CMT when patients develop severe chemotherapy-induced peripheral neurotoxicity upon use of vincristine. Desmoplastic nodular medulloblastoma may be successfully treated by chemotherapy without vincristine.

MAGNETIC RESONANCE IMAGING FEATURES OF PEDIATRIC MEDULLOBLASTOMA IN RELATION TO PATHOLOGICAL SUBTYPES

Medulloblastma (MB) is a highly malignant (WHO grade IV), primitive cerebellar tumor of neuroectodermal origin. Medulloblastomas have been classified, based on histopathological, biological, and clinical characteristics, into classic medulloblastoma (CMB), desmoplastic nodular medulloblastoma (DNMB), medulloblastoma with extensive nodularity and anaplastic/large cell medulloblastoma.Medulloblastoma shows heterogenous tumor features in each subtype. Based on these heterogeneity, magnetic resonance imaging (MRI) could differentiate pathological subtypes according to each imaging features. This study aimed to assess the relation between Magnetic Resonance imaging features of pediatric medulloblastoma and pathological subtypes to improve treatment outcomes of the disease.All patients were subjected to the following:o History taking.o Thorough clinical examination.o Conventional MRI study of the brain.o Susceptibility-weighted imaging of the brain with post processing phase image. The study was applied on a 1.5 Tesla Magnetom Avanto Siemens (left handed system) machine using conventional MRI sequences in addition to DWI. Imaging evaluation depended on tumor location, tumor enhancement and degree of tumor restriction on DWI. Histo-pathology remains the gold standard in differentiating subtypes, however we can use MRI in early prediction of the subtypes and early planning for their management, regardless MRI very important role in post-surgical assessment and follow up.

A Retrospective Analysis of the Demographics, Treatment, and Survival Outcomes of Patients with Desmoplastic Nodular Medulloblastoma Using the Surveillance, Epidemiology, and End Results (SEER) Database.

ObjectiveMedulloblastoma is the most common malignant brain tumor in children younger than four years of age. Children diagnosed with desmoplastic nodular medulloblastoma (DNMB) have more favorable survival outcomes when compared to other subtypes of this disease and, to date, the demographics of DNMB have only been characterized by a few small clinical case series. Additionally, the current effort is being made at reducing radiotherapeutic modalities in this patient population to avoid the adverse effects associated with radiotherapy in children. Therefore, the goal of this study was to characterize the demographics, treatments, and survival outcomes of patients with DNMB using a large federal database.MethodsThe Surveillance, Epidemiology, and End Results database was queried to retrieve demographical, treatment, and survival data for patients diagnosed with DNMB. Statistical testing was performed with the R software stats package (R Foundation for Statistical Computing, Vienna, Austria). Student’s t tests and analysis of variance tests were used to measure differences among survival rates.ResultsData from 360 patients with DNMB were retrieved from 1975-2016. There was a higher prevalence of DNMB in children younger than four years of age (33% of all cases). Males had a higher prevalence than females (57%). There was a preponderance of diagnoses in white individuals (82% of all cases) and more diagnoses in the Pacific Coast region (49% of all cases). Distant metastases were present at initial diagnosis in 8.7%. Surgery was performed in almost all patients, and gross total resection was achieved in 77%. The overall rate of survival was 77.8% at five years; age, sex, race, and geographical region of diagnosis were not associated with differences in survival outcomes. Patients with no radiotherapy had a lower rate of survival compared to patients with postoperative radiotherapy (mean difference = 19.7%; [95% CI 1.4%-38.0%], p = 0.0314). However, radiotherapy did not improve survival outcomes in patients undergoing chemotherapeutic treatment to a degree with any statistical significance. There was no statistically significant improvement in survival for patients undergoing radiotherapy prior to procedure when compared to patients with no radiotherapy.ConclusionsIn patients undergoing chemotherapeutic treatment for the DNMB subtype of medulloblastoma specifically, additional radiotherapy may offer only minimal benefit to the survival outcome. It is essential continued clinical trials be performed for the purpose of devising alternate treatments to radiotherapy.

Survival in adult and pediatric patients with medulloblastoma: A 2018 SEER-based analysis.

e14529 Background: Medulloblastoma (MB) is a malignant neuroectodermal tumor accounting for 30% of pediatric and only 1% of adult brain tumors. In previous studies comparing survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database no difference has been found. However, diagnostic subgroup analyses have been limited. Methods: We examined survival in children (age 0-19) and adults (20-79) coded as MB in the 2018 SEER database (2000-2016). We used Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n = 1,728). ICD 9473, supratentorial PNET (sPNET, n = 97) is biologically distinct and therefore it was analyzed separately. Results: We found that 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n = 488, 79.1%) (HR = 0.97, CI: 0.79 – 1.17, p = 0.50). Furthermore, subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n = 222, p = 0.09), large cell MB (n = 73, p = 0.46), or MB NOS (n = 1330, p = 0.10). Yet, children with sPNET had improved 5-year survival (n = 65, 72.3%) compared to adults (n = 29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p = 0.02,). These findings indicate that while survival in patients with MB is similar across age groups, children with sPNET have improved outcomes. Conclusions: In summary, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment (chemotherapy or radiation). For sPNET, the apparent improved outcomes for children merit further detailed investigation and will be re-evaluated using the new 2016 World Health Organization classification.

PDCT-03. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS

Abstract BACKGROUND/OBJECTIVE Survival had been poor in several multi-center/national studies since the 1980s attempting to delay, avoid or minimize brain irradiation in young children with medulloblastoma. The introduction of regimens in Germany incorporating both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, as well as regimens in North America incorporating marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), have reported encouraging outcomes. The objective of this report is to perform a comparative outcomes analysis of these differing strategies. METHODS Data from 17 prospective multi-center trials published between 1990 and 2018 for children under six years old with medulloblastoma were reviewed; event-free (EFS) and overall survivals (OS) were compared. RESULTS Two trials using full-dose cranio-spinal irradiation with or without chemotherapy reported 5-year survivals of 32–38%. Three trials using standard chemotherapy with delayed irradiation reported 2-4-year EFS and OS of 23–34% and 31–46%. Two trials employing standard chemotherapy without irradiation reported 3-5-year EFS and OS of 22–33% and 34–43%. Four trials incorporating HD-MTX with or without IVENT-MTX reported 5-10-year EFS and OS of 56–59% and 67–80%, and 31% and 59% respectively; one trial with HD-MTX without IVENT-MTX for localized desmoplastic/nodular medulloblastoma (DN-MB) reported 2-year EFS and OS of 52% and 92%. Finally, five trials employing induction chemotherapy, with or without HD-MTX, followed by single or tandem HDCx+AuHCR have reported 3-5-year EFS and OS of 45–60% and 60–70%. CONCLUSIONS The best survivals are observed in trials including HD-MTX and IVENT-MTX or including HD-MTX during induction followed by HDCx+AuHCR. Because histology/biology (classic and large cell/anaplastic versus DN-MB; SHH versus non-SHH subtypes) have crucial prognostic roles, EFS and irradiation-free survival advantages require analysis in these settings. The benefit of these trials appears true for all young children with medulloblastoma. Risk-adapted treatment stratification for young children may be improved by molecular profiling of SHH- and non-SHH medulloblastoma.

Desmoplastic nodular medulloblastoma in young children: a management dilemma.

Children with desmoplastic nodular medulloblastoma (DNMB) have excellent survival, leading multiple groups globally to attempt reduction of treatment-related morbidity. In 2013, the Children's Oncology Group began a clinical trial (ACNS1221) eliminating both radiation therapy (RT) and intraventricular methotrexate for children under 3 years of age with localized DNMB, aiming to build upon the excellent outcomes of the German HIT trials. ACNS1221 has recently closed due to increased incidence of recurrences noted at the 2-year interim analysis, raising important questions regarding optimal therapy for DNMB. A review of major clinical trials that included children with DNMB was performed through July 2017. One hundred and eighty-eight DNMB patients enrolled on 11 prospective clinical trials were identified. The use of marrow-ablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) or treatment with intraventricular methotrexate has been associated with excellent outcomes. RT was usually required for patients with evidence of disease at the end of therapy. The minimal intensity and duration of chemotherapy required to maximally cure children with DNMB without need of RT remains unknown. Further trials are required to better identify a subset of DNMB patients who can be cured without marrow-ablative chemotherapy or intraventricular methotrexate.

Clinical characteristics of children with medulloblastoma

Objective To investigate the clinical characteristics of children with medulloblastoma (MB). Methods The correlations amongst MB histopathological subtype, age at diagnosis, gender, primary tumor locations, relapsed tumor and relapsed tumor locations were analyzed retrospectively in 83 children who were diagnosed as MB by histopathology subtypes from February 2012 to April 2015 in Beijing Shijitan Hospital Affiliated to Capital Medical University.The data was conducted by using SPSS 22.0 statistical software. Results Among the 83 cases (53 boys and 30 girls), there were 14 patients younger than 3 years old (9 boys and 5 girls) and 69 patients (44 boys and 25 girls) older than 3 years old, including 28 relapsed (19 boys and 9 girls) and 55 non-relapsed cases (34 boys and 21 girls). The median age was 80.2 (13.1-184.7) months at diagnosis.Of these 83 cases, 48.2% (40/83 cases) was classic medulloblastoma (CMB) (2 cases less than 3 years old), 24.1% (20/83 cases) was desmoplastic/nodular medulloblastoma (DMB) (6 cases less than 3 years old), 12.1% (10/83 cases) was large cell/anaplastic medulloblastoma (LC/AMB) (1 case less than 3 years old), 3.6% (3/83 cases) was extensive nodular medulloblastoma (MBEN) (1 case less than 3 years old), and 12.1% (10/83 cases) (3 cases less than 3 years old) was mixed subtype.The relationships between age at diagnosis and histopathological subtype, gender and primary tumor location were all statistically significant (χ2=0.014, 0.013, all P<0.05). Conclusions The incidence of boys with MB is higher than girls.CMB is the main histopathologic subtype in children over 3 years old. The primary tumor location involving the cerebellar vermis or cerebellar vermis and the fourth ventricle is higher in girls with MB. The primary tumor location involving the fourth ventricle, the fourth ventricle and other parts of the central nervous system, Cerebellar vermis and other parts of the central nervous system or other parts of the central nervous system is higher in boys with MB. Key words: Histopathological subtype; Child; Medulloblastoma; Relapsed

Clinical, pathological, and molecular data on desmoplastic/nodular medulloblastoma: case studies and a review of the literature.

The aim of this study was to better define the clinical and biopathological features of patients with desmoplastic/nodular medulloblastoma (DNMB) and to further characterize this subgroup. 17 children aged < 5 years, with initial DNMB treated according to the HIT-SKK protocol, were evaluated. A retrospective central radiological review, a pathological and immunohistochemical study, and array-CGH and sequencing of germline SUFU and PTCH1 genes were performed. 15 histologically reviewed cases were confirmed as DNMB including three cases of medulloblastoma with extensive nodularity. Median age at diagnosis was 26 months. Radiology showed five cases with a vermis location and one with T2 hyperintensity. All cases showed a SHH immuno-profile. A 9q deletion was found in 6 cases, a MYCN–MYCL amplification in 1 case, and a SUFU germline mutation in 1 case (/9). The presence of SUFU and PTCH1 germline mutations agreed with previous reports. At 3 years, progression-free survival and overall-survival rates were 72 ± 15% and 85 ± 10%, respectively. The rate of recurrence was relatively high (4 patients). This may have been because chemotherapy was delayed in two cases. Age > 3 years, and residual tumor may also have been an explanation for recurrence.

PTPS-07COMPETING MOLECULAR GENETIC FORCES: TRISOMY 21(DOWN SYNDROME, DS) AND PTCH1 MUTATION (GORLIN SYNDROME) IN A 21 MONTH-OLD WITH SHH DESMOPLASTIC/NODULAR MEDULLOBLASTOMA

BACKGROUND: Individuals with Trisomy 21 have a striking cancer distribution, with a 10- to 20- fold increased risk of acute leukemia compared to a markedly decreased incidence of solid tumors. Medulloblastoma, the most common malignant brain tumor of childhood, is particularly rare in the DS population, with only one published case. As demonstrated in a mouse model of DS, the supernumerary chromosome 21 is associated with cerebellar hypoplasia and a decreased number of external granule cell layer progenitor cells (EGLs). Treatment of these mice with sonic hedgehog (Shh) signaling pathway agonists promotes normalization of EGLs and improved cognitive functioning. PATIENT: We describe a 21 month-old male with DS with desmoplastic/nodular medulloblastoma (DNMB) - a tumor derived from Shh dysregulation and over-activation of EGLs. Immunohistochemistry revealed patchy cytoplasmic GAB-1 staining and patchy strong YAP-1 nuclear and cytoplasmic staining, further placing this DNMB into the new consensus molecular classification Shh subgroup. Additional testing revealed a de novo heterozygous germ line mutation in the PTCH1 gene encoding a tumor suppressor protein in the Shh pathway; both parents tested negative for this mutation. CONCLUSIONS: The reduced presence of EGLs in DS patients offers a plausible explanation for the disparity of medulloblastoma in this population. Conversely, patients with PTCH1 germ line mutations experience Shh pathway overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) Syndrome and an increased incidence of malignant transformation of EGLs leading to medulloblastoma formation. This represents the first documented report of an individual with DS (developmental failure of EGLs, decreased incidence of medulloblastoma) simultaneously carrying PTCH1 germ line mutation (overstimulated EGLs, increased incidence of medulloblastoma). Thus, we observe a highly unusual circumstance in which the PTCH1 mutation appears to ‘trump’ the effects of trisomy 21 in causation of Shh-activated medulloblastoma. Additional genomic studies are ongoing and will be presented.

Cavernous angioma after chemotherapy for desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia

While cavernous angioma (CVA) after cranial irradiation has been documented, its development after high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has not. We present a patient with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED) who developed CVA 2 years after high-dose chemotherapy and PBSCT. A 1-year-old boy with ingravescent vomiting was admitted to our institute. He presented with a large head, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, and a bulging anterior fontanel. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications and severe obstructive hydrocephalus. The histological diagnosis of surgical specimens was DNMB, and he underwent postoperative multiple-drug chemotherapy with autologous PBSCT. The outcome was favorable and he did not undergo radiotherapy. After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA. To our knowledge, this is the first report of AED-associated DNMB and CVA.

Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB.

Desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia

We encountered a 1-year-old boy with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED). He was admitted to our institute because of ingravescent vomiting. On physical examination, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, enlarged head size, and bulging anterior fontanel were observed. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications. Severe obstructive hydrocephalus was also observed. He underwent surgery based on histologically diagnosed DNMB, and received postoperative multiple-drug chemotherapy with a completely favorable outcome. One year has passed and the disease-free patient is still doing well without any unwanted events. AED was diagnosed on the basis of the clinical findings: this is probably the first report on AED-associated DNMB.

Magnetic resonance imaging spectrum of medulloblastoma

Two medulloblastoma variants were recently added to the WHO classification of CNS tumours. We retrospectively analysed the imaging findings of 37 classic and 27 cases of variant medulloblastomas to identify imaging characteristics that might suggest a particular MB subtype. Sixty-four patients from three institutions were included. Location, tumour margins, signal intensities on conventional MRI, enhancement pattern, the presence of haemorrhage, calcifications and hydrocephalus were recorded and analysed. Signal characteristics on diffusion-weighted MR images and MR spectra were evaluated when available. Thirty-seven classic type of MB (CMB), twelve cases of desmoplastic/nodular medulloblastoma (DMB), nine medulloblastomas with extensive nodularity (MB-EN), five cases of anaplastic and one of large-cell medulloblastoma were included. Fifty of 64 tumours were located in the 4th ventricle region. On T2WI, CMB were all hyperintense, whereas DMB and MB-EN showed isointensity in up to 66%. One third of the classic MB showed only subtle marginal or linear enhancement. All medulloblastoma variants showed marked enhancement. The results of our study suggest: (a) an age-dependent distribution of MB variants, with DMB and MB-EN more common in younger children; (b) a female predominance in DMB; (c) a more common off-midline location in DMB (50%) and MB-EN (33%) variants.

Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis

To assess the prognostic role of clinical parameters and histology in early childhood medulloblastoma. Clinical and histologic data from 270 children younger than age 5 years diagnosed with medulloblastoma between March 1987 and July 2004 and treated within prospective trials of five national study groups were centrally analyzed. Two hundred sixty children with medulloblastoma and specified histologic subtype were eligible for analysis (median age, 1.89 years; median follow-up, 8.0 years). Rates for 8-year event-free survival (EFS) and overall survival (OS) were 55% and 76%, respectively, in 108 children with desmoplastic/nodular medulloblastoma (DNMB) or medulloblastoma with extensive nodularity (MBEN); 27% and 42%, respectively, in 145 children with classic medulloblastoma (CMB); and 14% and 14%, respectively, in seven children with large-cell/anaplastic (LC/A) medulloblastoma (P < .001). Histology (DNMB/MBEN: hazard ratio [HR], 0.44; 95% CI, 0.31 to 0.64; LC/A medulloblastoma: HR, 2.27; 95% CI, 0.95 to 5.54; P < .001 compared with CMB), incomplete resection and metastases (M0R1: HR, 1.86; 95% CI, 1.29 to 2.80; M+: HR, 2.28; 95% CI, 1.50 to 3.46; P < .001 compared with M0R0), and national group were independent prognostic factors for EFS, and OS. The HRs for OS ranged from 0.14 for localized M0 and DNMB/MBEN to 13.67 for metastatic LC/A medulloblastoma in different national groups. Our results confirm the high frequency of desmoplastic variants of medulloblastomas in early childhood and histopathology as a strong independent prognostic factor. A controlled de-escalation of treatment may be appropriate for young children with DNMB and MBEN in future clinical trials.