Advanced MRI Findings in Medulloblastomas: Relationship to Genetic Subtypes, Histopathology, and Immunohistochemistry

Abstract

BACKGROUND AND PURPOSE: For diagnosis of medulloblastoma, the updated World Health Organization classification now demands for genetic typing, defining more precisely the tumor biology, therapy, and prognosis. We investigated potential associations between magnetic resonance imaging (MRI) parameters including apparent diffusion coefficient (ADC) and neuropathologic features of medulloblastoma, focusing on genetic subtypes. METHODS: This study was a retrospective single-center analysis of 32 patients (eight females, median age = 9 years [range, 1-57], mean 12.6 ± 11.3) from 2012 to 2019. Genetic subtypes (wingless [WNT]; sonic hedgehog [SHH]; non-WNT/non-SHH), histopathology, immunohistochemistry (p53, Ki67), and the following MRI parameters were correlated: tumor volume, location (midline, pontocerebellar, and cerebellar hemisphere), edema, hydrocephalus, metastatic disease (presence/absence and each), contrast-enhancement (minor, moderate, and distinct), cysts (none, small, and large), hemorrhage (none, minor, and major), and ADC mean. The ADC mean was calculated using manually set regions of interest within the solid tumor. Statistics comprised univariate and multivariate testing. RESULTS: Out of 32 tumors, three tumors were WNT activated (9.4%), 13 (40.6%) SHH activated, and 16 (50.0%) non-WNT/non-SHH. Hemispherical location (n = 7/8, P = .003) and presence of edema (8/8; P < .001, specificity 100%, positive predictive value 100%) were significantly associated with SHH activation. The combined parameter "no edema + no metastatic disease + cysts" significantly discriminated WNT-activated from SHH-activated medulloblastoma (P = .036). ADC mean (10-6 mm 2 /s) was 484 for WNT-activated, 566 for SHH-activated, and 624 for non-WNT/non-SHH subtypes (P = .080). A significant negative correlation was found between ADC mean and Ki67 (r =-.364, P = .040). CONCLUSION: MRI analysis enabled noninvasive differentiation of SHH-activated medulloblastoma. ADC alone was not reliable for genetic characterization, but associated with tumor proliferation rate.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System: What Neuroradiologists Need to Know

“…The molecularly-defined MB subgroups are defined by DNA methylation or transcriptome profiling and remain unchanged: medulloblastoma, WNT-activated; medulloblastoma, SHH-activated and TP53 wild-type; medulloblastoma, SHH-activated and TP53-mutant; and medulloblastoma, non-WNT/non-SHH. 11, [37][38][39] Medulloblastoma, WNT-activated, represents approximately 10% of MBs. There are 2 age-determined subtypes: children and adults.…”

“…Metastases are rare at diagnosis, and the 5-year survival rate is 95%. 11, 37,38 Medulloblastoma, SHH-activated/ TP53 wild-type, represents approximately 30% of MBs overall but accounts for nearly two-thirds of MBs occurring between 3-16years of age. This MB subgroup has the most striking biologic, pathologic, and clinical heterogeneity of all 4 subgroups.…”

“…Desmoplastic MBs are more common in adults and have a predilection for the lateral cerebellar hemisphere. 37 SHH-3 and SHH-4 most commonly exhibit classic or large-cell anaplastic histology and can be found in all locations. 39,40 Medulloblastoma, SHH-activated/TP53-mutant, is the rarest of the MB subtypes and has the worst overall prognosis.…”

Dynamic susceptibility contrast and diffusion‐weighted MRI in posterior fossa pilocytic astrocytoma and medulloblastoma

“…To the best of our knowledge, this is the first study to demonstrate this correlation. There have been several reports indicating a correlation between lower ADC values and higher proliferation ability and consequently increased chromatin content in the tumor cells of MB 9,29,42 . In contrast, no significant correlation was demonstrated with DSC or between ADC values and PFS in patients with PA. Several mechanisms may be responsible, including the variety of histological characteristics of PA, as described above.…”

“…There have been several reports indicating a correlation between lower ADC values and higher proliferation ability and consequently increased chromatin content in the tumor cells of MB. 9,29,42 In contrast, no significant correlation was demonstrated with DSC or between ADC values and PFS in patients with PA. Several mechanisms may be responsible, including the variety of histological characteristics of PA, as described above. While high tumor perfusion parameters generally suggest an environment conducive to tumor growth, improved tumor perfusion also provides the opportunity to better respond to treatment by increasing the delivered chemotherapeutics to the tumor and improving the radiation effect by reducing hypoxia.…”