Large cell anaplastic medulloblastoma metastatic to the scalp: tumor and derived stem-like cells features

Abstract

BackgroundExtraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies.Case presentationWe present the case of a child with Large Cell Anaplastic (LC/A) MBL, who developed multiple subcutaneous metastases in the scalp area after a ventriculo-peritoneal shunting procedure. The disease rapidly progressed and the child died despite chemotherapy and primary tumour surgical debulking.We molecularly classified the tumour as a group 3 MBL; in addition, we derived stem-like cells (SLC) from a metastatic lesion. Primary tumour, metastases and SLC were further analysed, particularly focusing on features linked to the cutaneous dissemination. Indeed, molecules involved in angiogenesis, cell invasion and epidermal growth factor signalling resulted highly expressed.ConclusionsThe present report describes a very rare case of subcutaneous metastatic MBL. The tumour, metastases and SLC have been clinically, pathologically and molecularly characterized. Our case is an example of multidisciplinary approach aiming to characterize MBL aggressive behaviour.

Non-canonical Hedgehog/AMPK-Mediated Control of Polyamine Metabolism Supports Neuronal and Medulloblastoma Cell Growth

“…We next analyzed CNBP and ODC expression in a cohort of 42 human MBs, divided according to the molecular subgroup [5 WNT (wingless), 17 SHH (sonic hedgehog), 10 Group 3, and 10 Group 4] as previously described (Mastronuzzi et al, 2014; Miele et al, 2015). …”

Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup

“…We performed gene expression analysis of both hemispheric MB1 and vermian MB2 by real-time quantitative PCR (RT-QPCR). We used TaqMan Low Density Array custom designed with TaqMan assays (Life Technologies - Thermo Fisher Scientific, Waltham, MA USA) for genes of interest for medulloblastoma subgrouping, according to Northcott 2012 [ 36 , 37 ], while we used single TaqMan assay (Life Technologies - Thermo Fisher Scientific, Waltham, MA USA) for all other shown mRNA analyses [ 38 ]. Gene expression analysis on samples was performed using a ViiA7 sequence detection system according to the manufacturer’s instructions.…”

“…5 e). Both these events converge on shutting off oncosuppressor/differentiation genes and contribute to the maintenance of a more “cancer stem-like” phenotype [ 37 , 62 ].…”

Proteomic analysis of human sonic hedgehog (SHH) medulloblastoma stem-like cells

“…17 Stem cells or cancer stem-like cells (SLCs) represent a fraction of the tumor cell population which are not only the progenitors that give rise to MB 12 and sustain cancer growth, but have also been associated with poor prognosis in several kinds of tumors 18,19 by driving both resistance to therapy and disease relapse. 12,20 Molecular characterization of human malignant brain tumors, and in particular SLCs, has identified a broad spectrum of genes and molecular mechanisms inhibiting neuronal and glial differentiation. 21 We previously described SLCs derived from human SHH-MBs.…”