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

Abstract

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”.