Histological subtype of medulloblastoma frequently changes upon recurrence

Excerpt

Medulloblastoma (MB) is a malignant brain tumor that originates in the posterior fossa and comprises four subgroups reflecting distinct genetics, methylation patterns, gene expression and clinical prognosis (WNT, SHH, Group 3 and Group 4 MB) [5]. Differences in the histopathological appearance have long been the only criterion to categorize MB and still serve as a basis to diagnose “classic”, “desmoplastic/nodular”, “anaplastic”, “large-cell” or “extensively nodular” MB according to the current WHO classification of central nervous system tumors [3]. Some histological features are clearly enriched in certain MB subgroups, e.g., desmoplasia or extensive nodularity in SHH MB or anaplasia in Group 3 MB. However, histology may very well vary within one molecular subgroup of MB, indicating that MBs are distinct, even if they belong to the same molecular subgroup. For instance, within the group of SHH MBs, desmoplastic/nodular tumors have a significantly better clinical outcome than MB with classic histology [2]. Recent publications have now addressed the question, whether recurrences or metastases of MB belong to the same molecular subgroup as the primary tumor [1, 4, 6]. This is of tremendous clinical relevance with regard to the question whether, for instance, inhibition of the Sonic hedgehog or the Wnt pathway is still a reasonable therapeutic approach after relapse of a SHH or a WNT tumor. While the authors found that MB always stick to their original molecular subtype, no matter whether they recur at the primary site or whether they metastasize, detailed morphological tumor features have not been investigated. We analyzed 16 medulloblastoma cases, including classic and desmoplastic/nodular variants and all four molecular subgroups, each with samples of the primary tumor and the corresponding relapses (Fig. 1a). This included both local relapses as well as metastases (Fig. 1a).

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