Medulloblastoma with extensive nodularity: a variant with favorable prognosis

Giangaspero, Felice; Perilongo, Giorgio; Fondelli, M. P.; Brisigotti, Massimo; Carollo, C.; Burnelli, Roberta; Burger, Peter C.; Garrè, Maria Luisa

doi:10.3171/jns.1999.91.6.0971

Cited by 180 publications

(121 citation statements)

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“…This functional relationship is further supported when considering that medulloblastoma with extensive nodularity, which tend to show a lower SOX2 expression profile within the group of SHH medulloblastomas (Fig. 1E), are exclusively found in early childhood (32).…”

Section: Discussionmentioning

confidence: 60%

Sox2 Requirement in Sonic Hedgehog-Associated Medulloblastoma

et al. 2013

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The transcription factor Sox2 has been shown to play essential roles during embryonic development as well as in cancer. To more precisely understand tumor biology and to identify potential therapeutical targets, we thoroughly investigated the expression and function of Sox2 in medulloblastoma, a malignant embryonic brain tumor that initiates in the posterior fossa and eventually spreads throughout the entire cerebrospinal axis. We examined a large series of tumor samples (n ¼ 188) to show that SOX2 is specifically expressed in Sonic hedgehog (SHH)-associated medulloblastoma with an interesting preponderance in adolescent and adult cases. We further show that cerebellar granule neuron precursors (CGNP), which are believed to serve as the cell of origin for this medulloblastoma subgroup, express Sox2 in early stages. Also, Shh-associated medulloblastoma can be initiated from such Sox2-positive CGNPs in mice. Independent of their endogenous Sox2 expression, constitutive activation of Shh signaling in CGNPs resulted in significantly enhanced proliferation and ectopic expression of Sox2 in vitro and Sox2-positive medulloblastoma in vivo. Genetic ablation of Sox2 from murine medulloblastoma did not affect survival, most likely due to a compensatory overexpression of Sox3. However, acute deletion of Sox2 from primary cultures of CGNPs with constitutive Shh signaling significantly decreased proliferation, whereas overexpression of Sox2 enhanced proliferation of murine medulloblastoma cells. We conclude that Sox2 is a marker for Shhdependent medulloblastomas where it is required and sufficient to drive tumor cell proliferation. Cancer Res; 73(12); 3796-807. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 60%

Sox2 Requirement in Sonic Hedgehog-Associated Medulloblastoma

et al. 2013

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“…If also histology was considered, the vermis remained as the most frequent tumor site for most of the variants (100% for CMB, 83% for MBEN, and 80% for other variables) with the exception for DMB tumors where 6 of 10 tumors (60%) originated from the hemispheres. Seven of 12 cases (58%) with MBEN showed the typical MRI appearance described as ''grape like'' by Giangaspero et al (2); and reported by other authors (15,25).…”

Section: Resultsmentioning

confidence: 88%

“…MB variants have been better defined, and presently, some of them present clearly different aggressiveness. At one end of the spectrum, there are the anaplastic and large cell variants showing aggressive behavior (1,36), whereas at the other end, MBEN has been identified as occurring mainly in infants and having a favorable outcome (2). Histologically, MBEN contains large nodules with low proliferative activity and advanced neurocytic differentiation, as well as smaller areas with proliferative cells that are embedded in a dense reticulum fiber network.…”

Section: Discussionmentioning

confidence: 99%

“…Differentiation was assessed by immunostaining for neuron-specific enolase, synaptophysin, NeuN, GFAP, p75 low-affinity neutrophin receptor, and Ki-67 (MIB-1), as well as for myogenic markers. In accordance with the 2007 WHO classification and one of our previous publications, we defined MBEN as an MB in which there is (>50% of the examined tissue) histology of predominant nodularity, with intranodular nuclear uniformity within a desmoplastic background (1,2).…”

Section: Methodsmentioning

confidence: 99%

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Medulloblastoma Variants: Age-Dependent Occurrence and Relation to Gorlin Syndrome—A New Clinical Perspective

Garrè¹,

Cama²,

Bagnasco³

et al. 2009

Clinical Cancer Research

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Purpose: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). Experimental Design: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and. Results: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages V3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, LiFraumeni, and Fragile X) and 7 of these patients were ages V3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001). Conclusions: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages V3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS. Medulloblastoma (MB) with extensive nodularity (MBEN)occurring in young children is a rare but well-defined entity (1 -3). It is believed to be related to, but distinct from, desmoplastic MB (DMB). However, many aspects of this peculiar entity are still unclear, including its frequency, why it occurs at a very young age, why its prognosis is good, and its association with Gorlin syndrome (GS) or nevoid basal cell carcinoma syndrome. Most of the largest cooperative trials that have been published on MB in infants do not report on the relative frequency of this distinct entity compared with other variants and/or comment on the effect of the diagnosis of this variant on subsequent follow-up and treatment strategies (4 -6). A large prospective study by Eberhart reported that 73 of 330 (22%) cases had various degrees of desmoplasia and 14 of 330 cases were MBEN (4.2%; ref. 7). A more recent, extensive neuropathogical review focused on the morphologic features and biological behavior of 2 large contemporaneous cohorts of patients with MB and showed that DMB represents 5% of all MB and up to 57% of cases in children ages <3 years (3). A recent prospective, cooperative trial reported that desmoplastic histologic variants have a clearly favorable effect on prognosis in infants with MB who are treated with chemotherapy (CT) as first-line therapy. However, it did not mention the frequency of Imaging, Diagnosis, Pro...

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“…The specific neuroradiographic features of this medulloblastoma subtype are important to recognize as these patients have improved survival and may warrant the correct therapy [3,4].…”

Section: Introductionmentioning

confidence: 99%

A Rare Case of Medulloblastoma with Excessive Nodularity: Imagistic Features

Taşcu¹,

Rizea²

2014

Romanian Neurosurgery

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Medulloblastoma is the most common malignant tumor of childhood. Neuroimaging can play a role in the diagnosis of medulloblastoma, however atypical features do exist [2]. We report the case of a 1 year and 10-month-old infant diagnosed with a medulloblastoma with what we term "excessive" nodularity based on neuroimaging features and confirmed by neuropathology. CT-scan (CT) and magnetic resonance imaging (MRI) examination of the brain revealed a very large posterior fossa tumor attached to tentorium. On T2-weighted and post-gadolinium sequences, the tumor shows an extensive nodular grape-like appearance. Initial the patient was underwent a ventriculoperitoneal shunt.The second operative procedure was tumour resection. Histology examen revealed a diagnosis of medulloblastoma desmoplastic with extensive nodularity. The neuroradiographic features of this medulloblastoma with what we describe as "excessive" nodularity are important to recognize as these children may be cured with chemotherapy alone.

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Medulloblastoma with extensive nodularity: a variant with favorable prognosis

Abstract: Medulloblastomas with extensive nodularity represent a variant that is characterized by: 1) occurrence in very young children; 2) a peculiar grapelike appearance on neuroimaging; and 3) an apparently favorable outcome.

Cited by 180 publications

References 14 publications

Sox2 Requirement in Sonic Hedgehog-Associated Medulloblastoma

Sox2 Requirement in Sonic Hedgehog-Associated Medulloblastoma

Medulloblastoma Variants: Age-Dependent Occurrence and Relation to Gorlin Syndrome—A New Clinical Perspective

A Rare Case of Medulloblastoma with Excessive Nodularity: Imagistic Features

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