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Histopathology and molecular pathogenesis of medulloblastoma

Scott L Pomeroy, MD, PhD
Section Editors
Jay S Loeffler, MD
Patrick Y Wen, MD
Amar Gajjar, MD
Deputy Editor
April F Eichler, MD, MPH


Medulloblastomas are the most common malignant brain tumor of childhood and occur exclusively in the cerebellum. Histologically, they are highly cellular tumors with dark staining, round or oval nuclei. On a molecular level, medulloblastomas are heterogeneous and can be divided into four distinct subgroups with divergent tumor cell histology, genetics, clinical behavior, and patient outcomes.

The histopathology and molecular pathogenesis of medulloblastoma will be reviewed here. The clinical presentation, diagnosis, and treatment of medulloblastoma in children and adults, prognosis, and the delayed complications in survivors are discussed separately. (See "Clinical presentation, diagnosis, and risk stratification of medulloblastoma".)


At surgery, medulloblastomas are soft, friable tumors, often with necrosis. They are highly cellular tumors with abundant dark staining, round or oval nuclei, and little cytoplasmic differentiation. The spectrum of histopathologic appearance ranges from tumors with extensive nodularity to those with large cell/anaplastic features. The clinical outcome appears to be worse with increasing grade and extent of anaplasia [1]. Mitoses are often abundant, and neuroblastic Homer Wright rosettes can be found in up to 40 percent of cases [2,3].

Immunohistochemical studies most often demonstrate the expression of the neuronal markers synaptophysin and neuron specific enolase, and nestin, a marker of primitive neuroepithelial cells, consistent with their presumed origin from neuronal progenitors in the cerebellum [4]. Some medulloblastoma subtypes express markers specific for cerebellar granule cells [5,6], supporting the conclusion that they arise most often by oncogenic transformation of cerebellar granule cell progenitors; others express markers suggesting that they arise from multipotential progenitor cells from earlier stages of neural development. Nuclear β-catenin staining is present in most wingless (WNT) pathway tumors, and p53 immunostaining can be performed to identify tumors with TP53 mutations. (See 'Molecular subgroups' below.)

Several histologic variants of medulloblastoma have been described (figure 1 and table 1) [7]. The desmoplastic variant has abundant collagen and reticulin in the interstitial spaces as well as reticulin free "pale islands" [3]. This variant is associated with mutations in the patched-1 (PTCH1) gene on chromosome 9 and may have a better prognosis [8]. A second variant, the large cell/anaplastic (LCA) medulloblastoma, is characterized by cerebrospinal fluid dissemination and a more aggressive clinical course [9]. The LCA variant is most commonly associated with the group 3 molecular subtype in children and with group 4 tumors in adults. (See 'Group 3' below and 'Group 4' below.)


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Literature review current through: Dec 2016. | This topic last updated: Wed Aug 24 00:00:00 GMT+00:00 2016.
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