Diagnosis Of Medulloblastoma Research Articles

Molecular subgrouping and characterization analysis of medulloblastomas in a cohort of Japanese patients

Medulloblastoma is the most common solid malignancy and cause of oncologic death among children. Recent advances in genomic analysis obtained through international large-scale collaborations, Medulloblastoma Advanced Genomics International Consortium(MAGIC), have revealed that medulloblastomas can be classified into at least four distinct subgroups depending on their molecular expression profiles. These studies showed that the prognosis, age distributions, and molecular mechanisms of these subgroups of medulloblastomas completely differ from each other. Here we report the first analysis of molecular subgroups of medulloblastoma in Japanese patients(Shizuoka cohort). Molecular subgroups were predicted for 18 medulloblastomas;and age distributions, radiographic features, and histological characteristics were analyzed. It was predicted that 11% of the medulloblastomas were of the WNT type, 50% of the SHH type, 6% of the group 3 type, and 33% of the group 4 type. The percentage of group 3 type medulloblastomas was smaller than in the MAGIC study, while the percentage of the SHH type was larger. However, age distribution, recurrence-free survival, and overall survival for each group were quite similar to the MAGIC study. In addition, in an imaging study, 78% of patients with medulloblastomas of the SHH type presented tumors in the cerebellar hemispheres. The classical pathohistological hallmarks that may predict medulloblastoma prognosis were mainly seen in tumors of the SHH type. Molecular subgrouping of medulloblastomas could be important in the future, not only for prediction of prognosis, but also for decision making regarding the use of future new treatments such as molecular targeting therapy. The establishment of a public molecular analysis system of medulloblastomas in Japan is greatly desired, and it is currently under development;this database will help establish the molecular diagnosis of medulloblastomas in Japan.

髄芽腫の分子遺伝学的診断とその標準化

髄芽腫の分子遺伝学的診断とその標準化

GE-16 * JAPANESE PEDIATRIC MOLECULAR NEURO-ONCOLOGY GROUP (JPMNG): ESTABLISHMENT OF A NATIONWIDE MOLECULAR DIAGNOSTIC NETWORK FOR PEDIATRIC MALIGNANT BRAIN TUMORS IN JAPAN

Recent intensive molecular biological analyses revealed that pediatric brain tumors can be subclassified into multiple distinct molecular subgroups. The current consensus is that medulloblastomas consist of four core subgroups, and the sub-grouping of ependymomas is being proposed. This molecular sub-grouping system will not only improve our understanding of the biology of these tumors, but may also contribute for the development of novel therapeutic targets and strategies in the future. We have formed the Japanese Pediatric Molecular Neuro-oncology Group (JPMNG) and initiated a new clinical research project to establish a nationwide network of a molecular diagnosis system for pediatric brain tumors in Japan with the aim to provide a standardized molecular diagnosis according to the international consensus. We initially focus on medulloblastomas and ependymomas. Fresh, fresh-frozen and/or formalin-fixed paraffin-embedded archived tissue specimens are collected. Optimal diagnostic methods are being set up to reliably and reproducibly classify them into molecular subgroups according to the consensus criteria. These include gene expression analysis using the NanoString nCounter system, immunohistochemistry, RT-PCR, DNA sequencing, fluorescence in situ hybridization, and DNA methylation analysis. We have so far collected a total of 85 tissue samples including 30 medulloblastomas and 55 ependymomas. Preliminary study using 17 meduloblastomas indicated that proportions of four core subgroups were WNT (12%), SHH (35%), Group 3 (0%) and Group 4 (53%), respectively. Driver gene analysis showed that two WNT medulloblastomas had CTNNB1 mutations and TP53 mutations were found in one WNT and one SHH tumors. Mutation of TERT promoter was also found in one adult SHH tumors. We expect that this research will provide a highly accurate molecular diagnosis of medulloblastoma and ependymoma comparable to the international standard, leading to form a basis for better clinical management and outcomes and to develop new therapeutic strategies of the pediatric brain tumors in Japan.

A Rare Case of Medulloblastoma with Excessive Nodularity: Imagistic Features

Abstract Medulloblastoma is the most common malignant tumor of childhood. Neuroimaging can play a role in the diagnosis of medulloblastoma, however atypical features do exist [2]. We report the case of a 1 year and 10- month-old infant diagnosed with a medulloblastoma with what we term “excessive” nodularity based on neuroimaging features and confirmed by neuropathology. CT-scan (CT) and magnetic resonance imaging (MRI) examination of the brain revealed a very large posterior fossa tumor attached to tentorium. On T2-weighted and post-gadolinium sequences, the tumor shows an extensive nodular grape-like appearance. Initial the patient was underwent a ventriculo-peritoneal shunt. The second operative procedure was tumour resection. Histology examen revealed a diagnosis of medulloblastoma desmoplastic with extensive nodularity. The neuroradiographic features of this medulloblastoma with what we describe as “excessive” nodularity are important to recognize as these children may be cured with chemotherapy alone.

MRI surrogates for molecular subgroups of medulloblastoma.

Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups. All patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes. Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%-100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%-100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%-98%). When we used the MR imaging feature-based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort. Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing.

Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI

Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III-IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97% of all relapses occurred in the brain and 3% were isolated to the spine. Relapse was identified in 226 (8%) brain and 48 (4%) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care.

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

BackgroundMedulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy.ResultsOur study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset.ConclusionsOur results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors.

Relapse patterns in pediatric embryonal central nervous system tumors

Embryonal tumors of the central nervous system (CNS) share histological features and were therefore initially grouped as primitive neuroectodermal tumors (PNET) and treated similarly. We sought to determine the relapse patterns of specific embryonal CNS tumors. We conducted a historical cohort study of children diagnosed with CNS embryonal tumors from January 2000 to December 2011 in two pediatric neuro-oncology centers. Patients of 21 years of age or younger at time of presentation with a diagnosis of medulloblastoma, supratentorial PNET, pineoblastoma or atypical teratoid/rhabdoid tumor (ATRT) and at least one surveillance MRI were included. A total of 133 patients met inclusion criteria and 49 (37 %) patients relapsed during the observation period. The majority (79 %) of sPNET relapses were local, whereas all (100 %) PB relapses were associated with diffuse leptomeningeal disease. Relapse patterns for MB were more diverse with local recurrence in 27 %, distant recurrence in 35 % and diffuse leptomeningeal disease in 38 %. The frequency of relapses involving the spine differed (p < 0.001) between tumor types (MB 28/55 [51 %], sPNET 3/33 [9 %], ATRT 3/7 [43 %] and PB 12/12 [100 %]). No sPNET patients had isolated spinal relapse (0/14). Embryonal tumors were found to have divergent patterns of recurrence. While medulloblastoma has variable relapse presentations, sPNET relapses locally and pineoblastoma recurs with diffuse leptomeningeal disease involving the spine. These results point toward possibly new upfront treatment stratification among embryonal tumors in accordance with relapse pattern.

Chemotherapy for adult medulloblastoma: Is it necessary for all?

e13025 Background: Medulloblastome is rare in adults and treatment is usually extrapolated from the pediatric age group, the aim of our study is to highlight the importance of chemotherapy both in the concurrent and adjuvant setting in adult medulloblastoma. Methods: Fourty patients between 1995 and 2011 with diagnosis of medulloblastoma were treated at both the department of clinical oncology Cairo University or Nasser Institute Cancer Center, files reviewed for demographic characteristics, radiographic findings, extent of resection, staging, computerized tomography (CT) scans or magnetic resonance (MR), histopathology, treatment received, pattern of recurrence and treament received. All patients treated with craniospinal irradiation with total dose of 36Gy followed by a boost to the posterior fossa till 54Gy. Results: Fourty patient were identified from our medical records 24 (60%) male and 16 (40%) female, mean age 25 year (range = 18 - 45), 2 patients had residual tumor more than 2cm, one patient had leptomeningeal deposits, 13 patients had weekly vincristin 2 mg weekly followed by cisplatin vepside, 27 patients didn’t receive any form of chemotherapy. Five year overall and disease free survival for the whole group was 92% (95% CI: 88-142) , 66% (95% CI: 73-135) respectively, for patients received chemotherapy OAS and DFS was 80% (CI:71-138), and 68% (48-162) for patients didn‘t receive chemotherapy OAS and DFS was 90% (CI:81-161), and 67% (C: 58-101), No statistical significance difference of survival between the two groups. univariate analysis didnt show any statistical significance correlation with chemotherapy.G3 neutropenia was more in the chemotherapy group 6 patients vs. 1 patient in the chemotherapy group. Conclusions: Chemotherapy for adult medulloblastoma should be further investigated as good survival time can be achieved with radiotherapy alone. And recurrence can be still salvage with chemotherapy

Neuroradiological imaging features of infratentorial cranial fossa tumors in a child

Ependymoma is a rare tumor derived from the neuroepithelia, constituting about 39% of all central nervous system (CNS) tumors. In children, approximately two-thirds of such tumors occur in the infratentorial compartment while in adults the distribution is normally supratentorial. Ependymomas can be located either intracranially or intraspinally. Intracranial ependymomas occur more commonly in children, while intraspinal ependymomas predominate in adults. Sixty percent of tumors are located in the fourth ventricle of the infratentorial cranial fossa, which develop from the floor of the ventricle and may further extend into the foramen of Luschka and Magendie. Here we reported a case of ependymoma in the infratentorial cranial fossa with a differential diagnosis of medulloblastoma on head CT scan and MRI scan.

Malnutrition in pediatric patients with cancer at diagnosis and throughout therapy: A multicenter cohort study

Malnutrition is a common problem in pediatric patients with cancer. Reported prevalence varies widely and has often been assessed only in a subset of childhood types of cancer. This study aimed to describe the prevalence of malnutrition among pediatric patients newly diagnosed with cancer, to describe the occurrence and course of malnutrition during therapy and to identify factors associated with malnutrition during therapy. In a retrospective cohort study of 327 patients diagnosed from 2003 to 2006 in three Swiss tertiary care hospitals, weight and height measures together with patient-, disease-, and treatment-related characteristics were assessed. Malnutrition was defined as body mass index (BMI) below -2 standard deviation scores (SDS) or a weight loss >10% from diagnosis. Malnutrition was assessed at diagnosis and continuously during anticancer therapy. At diagnosis, 5.8% of the patients (19) were malnourished based on BMI. During anticancer therapy, the cumulative incidence of malnutrition rose to 22% (70 patients) after 30 days, to 36% (116 patients) after 60 days, and finally to 47% (155 patients). In these 155 patients, the median duration of malnutrition was 60 days (interquartile range, 21-122). Age above 10 years at diagnosis, BMI ≤ -1.0 SDS at diagnosis, and a diagnosis of medulloblastoma were positively associated with a higher proportion of malnutrition time during therapy. The rapid increase of malnutrition after the start of treatment underlines the need to develop evidence-based and efficient methods to provide nutritional support for children with cancer.

(1)H magnetic resonance spectroscopy and diffusion weighted imaging findings of medulloblastoma in 3.0T MRI: A retrospective analysis of 17 cases.

1H magnetic resonance spectroscopy and diffusion weighted imaging features of the cerebellar vermis in 17 medulloblastoma patients were retrospectively analyzed, and 17 healthy volunteers were selected as controls. 1H magnetic resonance spectroscopy showed that in all 17 medulloblastoma patients, N-acetyl aspartate and creatine peaks were significantly decreased, the choline peak was significantly increased, and there was evidence of a myo-inositol peak. Further, 11 patients showed a low taurine peak at 3.4 ppm, five patients showed a lipid peak at 0.9–1.3 ppm, and three patients showed a negative lactic acid peak at 1.33 ppm. Compared with the control group, the ratios of N-acetyl aspartate/choline and N-acetyl aspartate/creatine were significantly decreased, and the ratio of choline/creatine was increased, in medulloblastoma patients. Diffusion weighted imaging displayed hyperintensity and decreased apparent diffusion coefficient in medulloblastoma patients. These findings indicate that 1H magnetic resonance spectroscopy and diffusion weighted imaging are useful for qualitative diagnosis of medulloblastoma.

Long time to diagnosis of medulloblastoma in children is not associated with decreased survival or with worse neurological outcome.

BackgroundThe long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae.Patients and MethodsThis retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome.ResultsThe median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31–121, range 3–457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup.ConclusionsWe found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims.

Medulloblastoma with Excessive Nodularity: Radiographic Features and Pathologic Correlate

Medulloblastoma with extensive nodularity is a rare subtype of the most common malignant childhood brain tumor and has been associated with more favorable prognosis. The authors report the case of a 10-month-old girl with a posterior fossa tumor of excessive nodularity with decreased diffusivity on diffusion-weighted magnetic resonance imaging sequences and robust grape-like postgadolinium contrast enhancing features. The unique neuroradiographic features were confirmed by histopathology and a diagnosis of medulloblastoma with extensive nodularity was made. This case highlights the importance of recognizing this unique medulloblastoma subtype preoperatively, as the more favorable outcome may preclude less aggressive medical management.

Medulloblastoma Presenting With Pure Word Deafness: Report of One Case and Review of Literature

Pure word deafness (PWD) is a rare disorder characterized by impaired verbal comprehension sparing discrimination and recognition of nonverbal sounds with relatively normal spontaneous speech, writing, and reading comprehension. Etiologies of this syndrome are varied, and there are rare reports about brain tumor with PWD in children. We report a case of medulloblastoma presented with PWD in a 7-year-old girl. She visited our outpatient clinic because of English dictation performance deterioration. PWD was diagnosed by the otolaryngologist after examinations. Posterior fossa tumor and obstructive hydrocephalus were shown in the magnetic resonance imaging of the brain. The diagnosis of medulloblastoma was then made by pathology.

Superficial Siderosis: A Case Report

Superficial siderosis of the central nervous system is the result of chronic recurrent hemorrhages (e.g., arteriovenous malformations, tumors, or trauma), which leads to the accumulation of cytotoxic hemosiderin and presents with hearing loss, cerebellar dysfunction, and myelopathy. This article presents a clinical case of an 11-year-old boy in whom the diagnosis of medulloblastoma was established. He underwent surgery, and after a few years, he began to complain of hearing loss. Magnetic resonance imaging revealed the cause of the hearing disturbance. The aim of this article is to review the recent literature related to the etiology, clinical and radiologic features of superficial siderosis, emphasizing the role of magnetic resonance imaging.

Second malignant tumors in childhood cancer survivors.

9573 Background: The risk of second malignancies is 3-6 times more in childhood cancer survivors. The 20 year cumulative risk of secondary malignancies in 14,193 chilhood cancer survivors followed for >5 years was 3.2% (Cancer 2005). Methods: 1,500 childhood cancer survivors treated between 1990-2010 in the Istanbul University, Oncology Institute were evaluated for second malignancies. Results: 16 second malignancies were identified in 15 childhood cancer survivors in a median time of 6 years. The 16 second malignancies were: 4 acute myeloblastic leukemias (AML), 2 malignant nerve sheath tumors (MNST), 8 sarcomas, 2 breast cancers. AML was diagnosed in 4 children in a median of 31 months (13-60 mo): The primary diagnosis were Ewing’s sarcoma, osteosarcoma, non-Hodgkin’s lymphoma and neuroblastoma. Two of these children had recieved multiple therapies for recurrences. Two children with a primary diagnosis of medulloblastoma and neuroblastoma developed MNST in the radiation field after 9 years. A Ewing sarcoma patient developed sarcoma after 6 years, an osteosarcoma patient developed breast cancer after 8 years, an ALL patient developed Ewing sarcoma after 3 years, a mesenchymal chondrosarcoma patient developed breast cancer after 11 and osteosarcoma after 16 years. These were not in the radiation field. A soft tissue sarcoma, and an osteosarcoma developed in two bilateral retinoblastoma patients both after 14 years, a sarcoma developed in a rabdomyosarcoma patient after 6 years and in a patient treated for nasopharyngeal carcinoma after 3.5 years all in the radiation field. An extremity osteosarcoma developed in another bilateral retinoblastoma patient after 4 years. The two patients that developed breast cancer and the six patients that developed sarcoma are alive. All others are dead of disease. Conclusions: The risk of secondary malignancies in our series is 1% and low in comparison to the literature. However, it has increased within years and may still increase as the follow-up time increases. Since, the risk of second malignancies is associated with the cumulative dose of some chemotherapeutics, the radiation dose/field, the use of minimal therapy that has the maximum efficacy according to the diagnosis, age, stage and risk of the patient is important.

Interval between onset of symptoms and diagnosis of medulloblastoma in children: distribution and determinants in a population-based study

Hospital-based studies have reported long delays in the diagnosis of paediatric brain tumours. Our objective was to describe the duration between onset of symptoms and diagnosis of medulloblastoma in children and study their clinical determinants in a population-based study. This retrospective cohort study included all paediatric medulloblastoma from a region of France from 1990 to 2005. The median interval from symptom onset until diagnosis for these 166 patients was 65 days and did not decrease during the study period. The most frequent manifestations were: vomiting (88%), headaches (79%), psychomotor regression (60% of children under 3 years), psychological symptoms (27%), strabismus (26%), and asthenia (25%). For one third of the children under 3 years, the diagnosis was made only after life-threatening signs of intracranial hypertension appeared. The prediagnosis interval was significantly longer (median 91 vs. 60 days, p = 0.001) in children with psychological symptoms (27%). Causes for intervals that exceeded the median (65 days) included inconsistent (25%) or late (36%) combination of headaches and vomiting, a period of spontaneous symptom remission (14%-20%), no (24%) or late (57%) neurological signs, psychological symptoms (35%), and a normal neurological examination (27%). Time to medulloblastoma diagnosis in children remains fairly long, despite advances in imaging. Primary-care physicians must be suspicious not only of suggestive neurological signs, but also of non-specific symptoms that persist or are multiple. A meticulous neurological examination and cerebral imaging for such patients might facilitate earlier diagnosis.

Magnetic resonance spectroscopy findings in non-enhancing desmoplastic medulloblastoma

Medulloblasoma is a common posterior fossa tumor seen in children and presents with some typical features like midline vermian location and fairly homogeneous enhancment. Desmoplastic variety of medulloblastoma is usually seen in the adults and is known to show some atypical features like lateral cerebellar location, variable enhancement, and early meningeal infilteration. Therefore medulloblastoma should always be considered in differential diagnosis of posterior fossa mass in adults even when typical imaging findings are not that of medulloblastoma. Enhancement pattern can be variable in these tumors varying from mild to striking. Occasionally, totally non-enhancing tumors are encountered, which can cause further diagnostic confusion. We describe the magnetic resonance (MR) and MR spectroscopy findings in a case of midline vermian mass, which did not show any enhancement on post-contrast images, and was subsequently proven to be desmoplastic medulloblastoma. On MR spectroscopy, the mass showed elevated choline peak consistent with mitotic lesion. No significant lipid lactate leak was seen, which is also consistent with the ususally homogeneous nature of these tumors. Moreover, it displayed taurine peak at 3.4 ppm which is considered fairly specific for medulloblastoma. Therefore, MR spectroscopy findings can be helpful in the diagnosis of medulloblastoma in adults when MR imaging findings can be nonspecific.

Cerebrospinal fluid M staging for medulloblastoma: Reappraisal of Chang's M staging based on the CSF flow

Tumor seeding is a strong negative prognostic factor for patients with medulloblastoma. Because Chang's M staging is based primarily on CT and myelographic findings and might be contradictory to the direction of normal cerebrospinal fluid (CSF) flow, seeding patterns and appropriate staging of medulloblastoma need to be revisited in patients diagnosed in the MRI era. We retrospectively reviewed the clinical and radiological data of 86 patients with a diagnosis of medulloblastoma who were treated in the MRI era. The presence of seeding in each subarachnoid space compartment and the patterns of seeding were analyzed in correlation with patient survival data. Thirty-four patients had gross seeding on perioperative MRI. Thirty-two patients had seeding in the spinal compartment. Sixteen and 12 patients had seeding in the infratentorial and supratentorial compartments, respectively. There was an apparent hierarchy of seeding (ie, from seeding in the spinal compartment up to the supratentorial compartment). Patients with seeding in the spinal compartment had longer progression-free survival (P = .038) and a tendency toward better overall survival (P = .053) compared with patients with seeding in intracranial compartments. We modified Chang's M staging based on the CSF flow and termed this approach "CSF M staging." CSF M staging for medulloblastoma, in which intracranial seeding occupies a higher rank than spinal seeding, was a better predictor of patient prognosis. This modified staging method may be applied to metastatic staging of brain tumors located in the fourth ventricle.