Gangliogliomatous maturation in cerebellar medulloblastoma

Kane, Walter C.; Aronson, Stanley M

doi:10.1007/bf00687936

Cited by 24 publications

(5 citation statements)

References 8 publications

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“…Interestingly, we observed apoptosis at baseline in GTML tumors, an event commonly associated with transformation by Myc family genes (Evan et al 1992;Nesbit et al 1998). Withdrawal of Mycn led to senescence of tumor cells, a result aligned with clinical observations demonstrating both quiescence and differentiation in human MB after therapy (Kane and Aronson 1967;Kudo et al 1990;Cai et al 2000). The GTML mouse provides an ideal system in which to investigate high-risk subclasses of human MB.…”

Section: Discussionsupporting

confidence: 59%

Pleiotropic role forMYCNin medulloblastoma

Swartling¹,

Grimmer²,

Hackett³

et al. 2010

Genes Dev.

153

191

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Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Sonic Hedgehog (SHH) signaling drives a minority of MB, correlating with desmoplastic pathology and favorable outcome. The majority, however, arises independently of SHH and displays classic or large cell anaplastic (LCA) pathology and poor prognosis. To identify common signaling abnormalities, we profiled mRNA, demonstrating misexpression of MYCN in the majority of human MB and negligible expression in normal cerebella. We clarified a role in pathogenesis by targeting MYCN (and luciferase) to cerebella of transgenic mice. MYCN-driven MB showed either classic or LCA pathologies, with Shh signaling activated in~5% of tumors, demonstrating that MYCN can drive MB independently of Shh. MB arose at high penetrance, consistent with a role for MYCN in initiation. Tumor burden correlated with bioluminescence, with rare metastatic spread to the leptomeninges, suggesting roles for MYCN in both progression and metastasis. Transient pharmacological down-regulation of MYCN led to both clearance and senescence of tumor cells, and improved survival. Targeted expression of MYCN thus contributes to initiation, progression, and maintenance of MB, suggesting a central role for MYCN in pathogenesis.

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Section: Discussionsupporting

confidence: 59%

Pleiotropic role forMYCNin medulloblastoma

Swartling¹,

Grimmer²,

Hackett³

et al. 2010

Genes Dev.

153

191

View full text Add to dashboard Cite

show abstract

“…In this case report we showed that neuronal maturation may occur also in adult MB patients. Tumor maturation is associated with better prognosis in neuroblastoma [9,10] and in pediatric MB [12][13][14]. Similarly, after a long follow up, our adult patient was alive and free from disease progression.…”

Section: Discussionsupporting

confidence: 56%

“…The treatment for MB in adults is represented by surgical resection followed by radiotherapy (36 Gy in 20 fractions, followed by a boost of 18 Gy in 10 fractions to the posterior fossa, up to a total of 54 Gy), adding chemotherapy for high-risk patients. Post therapeutic neuronal maturation is a rare event that can occur in some pediatric neoplasms, such as neuroblastoma and MB [9][10][11][12][13][14]. Here we report the long term follow up of an adult MB that experienced post-therapy neuronal maturation and a favorable outcome.…”

Section: Introductionmentioning

confidence: 99%

Histopathologic Modification in CNS Neuroectodermal Tumor: A Long Term Follow Up of a Clinical Case

Franceschi¹,

Bartolotti²,

B??R??³

et al. 2018

Med Case Rep

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Background:Post-therapy differentiation in medulloblastoma (MB) is a rare event that has been described only in pediatric age. Methods:We describe the long term follow up of a case of medulloblastoma maturation after chemotherapy and radiotherapy in an adult MB patient. Results and Discussion:A 20-year-old patient was partially resected of a MB with ki-67 of 60%. DNA methylation-derived subgroup showed a molecular SHH profile. The patient received cranio-spinal tomotherapy (32.4 Gy in 18 fractions) with a boost on posterior fossa (23.4 Gy in 17 fractions, total dose: 55.8 Gy in 32 fractions). The MRI performed 2 months after revealed a minimal volumetric increase. The patient underwent 2 cycles of Cisplatin -Etoposide chemotherapy. The MRI showed stable disease. The patient underwent second surgery. The specimen showed neuronal cells showing various degrees of maturation from neurocytic to ganglion cells. No embryonal cells were present. Mitoses were absent. The residual lesion showed the post-therapy neuronal maturation of a medulloblastoma. DNA methylation-derived subgrouping confirmed the SHH profile. No other treatments were delivered after the second resection. To date the patient is still alive and free from progression 54 months after primary surgery. Conclusion:After a long term follow up, we showed that tumor maturation in an adult patient with medulloblastoma is characterized by a favorable outcome. Physicians should take into account that tumor maturation may occur and that its recognition is essential to define the prognosis and to manage adult patients.

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“…The principle that embryonic tumors, such as the medulloblastoma (embryonic tumors being defined as those originating in cells that are still immature), may differentiate into more mature, less malignant neoplasms, has been discussed for many decades (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The lessened malignancy implies that, when mature, the t u m o r grows more slowly, destroys the normal tissues to a lesser degree, and permits the patient to live for a longer time.…”

Section: Discussionmentioning

confidence: 99%

Extensive advanced maturation of medulloblastoma to astrocytoma and ependymoma

1983

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Four cases of medulloblastoma in children are reported in which a marked degree of differentiation towards neoplastic adult glioma cells was observed. The original immature and highly malignant tissue had largely disappeared in three and completely disappeared in the fourth. The mature tissues which replaced them included astrocytoma tissues in all four, but ependymoma tissues predominated in two. These cases illustrate a general principle applicable to embryonic tumors, defined as those originating in cells that are still immature. Such maturation and differentiation are presumably associated with a decrease in growth rate and an improved prognosis. A continuation of the process of maturation may account for the unexpectedly favorable course sometimes noted with gliomas in children. The processes of differentiation, dedifferentiation, and anaplasia are discussed, particularly the semantic implications of the terms, and it is suggested that the term "dedifferention" is unfortunate since it may have two different meanings. It may be used as a synonym of anaplasia, or it may imply a progression of change backward on the embryologic pathways along which primitive cells normally mature. The latter may not occur, but the assumption that it does leads to views concerning the glioma group as a whole and the phenomena described in this paper, which we hold to be untentable.

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Gangliogliomatous maturation in cerebellar medulloblastoma

Cited by 24 publications

References 8 publications

Pleiotropic role forMYCNin medulloblastoma

Pleiotropic role forMYCNin medulloblastoma

Histopathologic Modification in CNS Neuroectodermal Tumor: A Long Term Follow Up of a Clinical Case

Extensive advanced maturation of medulloblastoma to astrocytoma and ependymoma

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