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Background
This is a rare and aggressive tumor of the brain that usually occurs in children or young adults. These tumors typically occur in an infratentorial location, below the tentorium cerebelli in the brain. It can spread from the brain to the spine or to other parts of the body.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare AGE RANGE-MEDIAN Childhood
DISEASE ASSOCIATIONS CHARACTERIZATION MALIGNANT RHABDOID TUMOR
Medulloblastoma associated with malignant rhabdoid tumor of the kidney: case report.Watanabe K, Wakai S, Kumakura N, Kurosu A, Nagai M, Tsuchioka T, Fujiwara T.
Department of Neurosurgery, Dokkyo University School of Medicine.
Noshuyo Byori 1993;10(1):75-9 Abstract quote The authors report a case of 6-month-old boy with cerebellar medulloblastoma associated with malignant rhabdoid tumor of the kidney, presenting with an abdominal mass, large head and projectile vomiting.
Following removal of the renal tumor, the mass arising from the superior vermis about 6 cm in diameter was removed by a combined right occipital transtentorial and suboccipital approach. The patient had been well for 3 months after surgery followed by chemotherapy but died eventually of tumor recurrence in the abdomen.
Reported cases of malignant rhabdoid tumor of the kidney associated with brain tumor are reviewed and its characteristics are discussed.
RUBINSTEIN-TAYBI SYNDROME
Medulloblastoma in a child with Rubenstein-Taybi Syndrome: case report and review of the literature.Taylor MD, Mainprize TG, Rutka JT, Becker L, Bayani J, Drake JM.
The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 Canada.
Pediatr Neurosurg 2001 Nov;35(5):235-8 Abstract quote Although medulloblastoma is usually sporadic, there are a number of uncommon predisposing germline mutation syndromes, including: Gorlin's Syndrome, Turcot's Syndrome and Li-Fraumeni Syndrome. Patients with Rubenstein-Taybi Syndrome secondary to mutation/deletion of the CBP gene on chromosome 16 are predisposed to a variety of developmental anomalies as well as cancer.
We report a child with Rubenstein-Taybi syndrome who developed a cerebellar medulloblastoma and review the literature on Rubenstein-Taybi Syndrome and pediatric medulloblastoma. As the product of the CBP gene functions in a variety of signaling pathways, we discuss the molecular implications of findings a medulloblastoma in a child with Rubenstein-Taybi Syndrome.
PATHOGENESIS CHARACTERIZATION ANGIOGENESIS
Angiogenic profile of childhood primitive neuroectodermal brain tumours/medulloblastomas.Huber H, Eggert A, Janss AJ, Wiewrodt R, Zhao H, Sutton LN, Rorke LB, Phillips PC, Grotzer MA.
Division of Oncology, The Children's Hospital of Philadelphia, PA 19104, USA.
Eur J Cancer 2001 Nov;37(16):2064-72 Abstract quote Primitive neuroectodermal brain tumours (PNET) including medulloblastomas (PNET/MB) are the most common malignant brain tumours of childhood. Similar to many other brain tumours, PNET/MB often show marked neovascularisation.
To determine which angiogenic factors contribute to PNET/MB angiogenesis, we examined the expression of eight angiogenic factors (vascular endothelial growth factors (VEGF, VEGF-B, VEGF-C), basic fibroblast growth factor (bFGF), angiopoetins (Ang-1, Ang-2), transforming growth factor (TGF-alpha), and platelet-derived endothelial growth factor (PDGF-A)) by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in six PNET cell lines and 28 primary PNET/MB. Expression levels of angiogenic factors were compared with microvessel density, TrkC mRNA expression, clinical variables and survival outcomes.
Our results indicate that all PNET/MB tested produce a wide range of angiogenic factors that are, individually or together, likely to play a direct role in PNET/MB tumour growth. This suggests that anti-angiogenesis approaches targeting VEGF alone may be insufficient in PNET/MB.
CHROMOSOMAL ABNORMALITIES
Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas.Eberhart CG, Kratz JE, Schuster A, Goldthwaite P, Cohen KJ, Perlman EJ, Burger PC.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Brain Pathol 2002 Jan;12(1):36-44 Abstract quote We correlate chromosomal changes in medulloblastomas with histologic subtype, reporting the analysis of 33 medulloblastoma specimens by comparative genomic hybridization, and a subset by fluorescence in situ hybridization.
Of the 33 tumors, 5 were desmoplastic/nodular, 10 were histologically classic, and 18 were large cell/anaplastic. Chromosomal gains and losses were more common in anaplastic medulloblastomas than in non-anaplastic ones.
We identified 4 medulloblastomas with c-myc amplification and 5 medulloblastomas with N-myc amplification; all 9 were of the large cell/anaplastic subtype. Additional regions with high level gains included 2q14-22, 3p23, 5p14-pter, 8q24, 9p22-23, 10p12-pter, 12q24, 12p11-12, 17p11-12, and Xp11. The majority of these high level gains occurred in anaplastic cases. We also found loss of chromosome 17p in 7 large cell/anaplastic cases but no nonanaplastic medulloblastomas. Finally, we detected a significantly increased overall number of chromosomal alterations in large cell/anaplastic medulloblastomas (6.8/case) compared to non-anaplastic ones (3.3/case).
These findings support an association between myc oncogene amplification, 17p loss, and large cell/anaplastic histology.
Genetic alterations in childhood medulloblastoma analyzed by comparative genomic hybridization.Michiels EM, Weiss MM, Hoovers JM, Baak JP, Voute PA, Baas F, Hermsen MA.
Department of Pediatric Oncology, Emma Kinderziekenhuis/Academic Medical Center, Amsterdam, The Netherlands.
J Pediatr Hematol Oncol 2002 Mar-Apr;24(3):205-10 Abstract quote Despite intensive therapy, the survival of children with medulloblastoma remains disappointing. Moreover, children who survive are affected by serious long-term sequelae of treatment that impair their quality of life.
In search of chromosomal aberrations indicative of sites involved in oncogenic transformation and in an attempt to find reliable prognostic markers, the authors analyzed 15 medulloblastomas by comparative genomic hybridization. All neoplasms showed chromosomal abnormalities. The most frequent losses were 17p (7/15 tumors), 8p and 11p (6/15), 10p, 1lq, 16q, and 20q (5/15), and 20p (4/15). Gains were recurrently found at 7q (10/15 tumors), 17q and 18q (9/15 tumors), 7p and 13q (7/15), 18p (6/15), and 1q, 4q, 6q. and 9p (5/15 tumors). Four tumors showed loss of 17p together with gain of 17q, suggesting an isochromosome 17q. High-level amplifications were seen at 1p34, 5p15, 13q34, and 18p11 (one tumor each), and at 2p15 in two tumors, one of which was proven to be N-Myc amplification.
The overall pattern of alterations found in this study confirms the findings of other studies and adds two novel regions with chromosomal gains, at 13q and 18q. Previous reports on the relation between 17q gain and survival could not be confirmed, whereas amplification of N-myc or L-myc seems to indicate poor clinical outcome.
Comprehensive molecular cytogenetic investigation of chromosomal abnormalities in human medulloblastoma cell lines and xenograft.Aldosari N, Wiltshire RN, Dutra A, Schrock E, McLendon RE, Friedman HS, Bigner DD, Bigner SH.
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Neuro-oncol 2002 Apr;4(2):75-85 Abstract quote Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors.
Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridization to study 4 medulloblastoma cell lines and 1 xenograft. Cell line D-425 Med had a relatively simple karyotype, with a terminal deletion of 10q and amplification of MYC in double-minutes (dmins). FISH demonstrated that an apparent isochromosome (17q) by routine karyotyping was actually an unbalanced translocation between 2 copies of chromosome 17. Cell line D-556 Med also had a simple near-diploid stemline with an unbalanced 1;13 translocation resulting in a gain of 1q, an isochromosome (17q), and dmins.
These findings were initially described using routine G-banded preparations, and FISH showed that the dmins were an amplification of MYC and the i(17q) was an isodicentric 17q chromosome. The other finding was confirmed by FISH, SKY, and comparative genomic hybridization. Cell lines D-721 Med and D-581 Med had complex karyotypic patterns that could be completely characterized only when FISH and SKY were used. Xenograft D-690 Med also had a complex pattern that FISH and SKY were helpful in completely elucidating. Interestingly, balanced reciprocal translocations were seen as well as complicated unbalanced translocations and marker chromosomes. Comparative genomic hybridization demonstrated only a deletion of 10q22-10q24, supporting the idea that despite the complexity of the chromosomal rearrangements, minimal alterations in the overall chromosomal content had occurred.
This study demonstrates that routine cytogenetic preparations are adequate to describe chromosomal abnormalities in occasional medulloblastoma samples, but a broader spectrum of molecular cytogenetic methods is required to completely analyze most of these tumor samples.
ONCOGENE
Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.MacDonald TJ, Brown KM, LaFleur B, Peterson K, Lawlor C, Chen Y, Packer RJ, Cogen P, Stephan DA.
Center for Cancer and Transplantation Biology, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC, USA.
Nat Genet 2001 Oct;29(2):143-52 Abstract quote Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome.
We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expression differed significantly between classes. Using a class prediction algorithm based on these genes and a leave-one-out approach, we assigned sample class to these tumors (M+ or M0) with 72% accuracy and to four additional independent tumors with 100% accuracy. We also assigned the metastatic medulloblastoma cell line Daoy to the metastatic class. Notably, platelet-derived growth factor receptor alpha (PDGFRA) and members of the downstream RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors shows significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, we show that platelet-derived growth factor alpha (PDGFA) enhances medulloblastoma migration and increases downstream MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK1 (p42 MAPK) and MAPK3 (p44 MAPK) phosphorylation in a dose-dependent manner. Neutralizing antibodies to PDGFRA blocks MAP2K1, MAP2K2 and MAPK1/3 phosphorylation, whereas U0126, a highly specific inhibitor of MAP2K1 and MAP2K2, also blocks MAPK1/3. Both inhibit migration and prevent PDGFA-stimulated migration.
These results provide the first insight into the genetic regulation of medulloblastoma metastasis and are the first to suggest a role for PDGFRA and the RAS/MAPK signaling pathway in medulloblastoma metastasis. Inhibitors of PDGFRA and RAS proteins should therefore be considered for investigation as possible novel therapeutic strategies against medulloblastoma.
MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ hybridization study on paraffin sections from the Children's Oncology Group.Aldosari N, Bigner SH, Burger PC, Becker L, Kepner JL, Friedman HS, McLendon RE.
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Arch Pathol Lab Med 2002 May;126(5):540-4 Abstract quote CONTEXT: Brain tumors are the most common solid tumor in childhood, and medulloblastoma is the most common malignant brain tumor in this age group. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC (c-myc), amplification of MYCN (N-myc), and isochromosome 17q. Data on these tumors indicate that the frequency of MYCC amplification is 5% to 10%. Fluorescence in situ hybridization is a powerful tool for investigating these features on archival material.
OBJECTIVES: To determine if intratumoral heterogeneity exists for MYCC and MYCN in medulloblastomas and if tumors with amplified MYCC or MYCN exhibit consistent histologic patterns.
DESIGN: In this fluorescence in situ hybridization study, we investigated the frequency and prognostic significance of MYCC and MYCN amplification in 77 medulloblastomas derived from the Children's Oncology Group.
RESULTS: MYCC amplification occurred in only 4 (5.2%) of 77 tumors. The 4 patients died of clinically aggressive neoplasms within 7 months of diagnosis. Similarly, 4 of 77 patients' tumors were found to exhibit MYCN amplification, but survival data are incomplete at present, therefore prognostic significance cannot be characterized.
CONCLUSIONS: These data establish the frequency of MYCC amplification in a large cohort of children with medulloblastoma and further suggest that MYCC amplification may be a marker of poor prognosis. Intratumoral heterogeneity was identified for these oncogenes in that 1 patient's tumor exhibited evidence of both MYCN and MYCC amplification, and this patient experienced a shortened survival time.
LABORATORY/RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC Medulloblastoma with extensive calcification.
Prasad A, Madan VS, Buxi TB, Prasad ML.
Department of Neurosurgery, Sir Ganga Ram Hospital, New Delhi.
Neuroradiology 1991;33(5):447-8 Abstract quote Calcification in cases of medulloblastoma has been described with varying frequency (10%-15.4%) on computed tomographic (CT) scan. Usually these calcifications are small in size and speckled.
The authors report a case of medulloblastoma with extensive calcification in the lateral hemisphere of the cerebellum in an 18-year-old boy.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS ADULT
Adult cerebellar medulloblastomas: the pathological, radiographic, and clinical disease spectrum.Hubbard JL, Scheithauer BW, Kispert DB, Carpenter SM, Wick MR, Laws ER Jr.
Department of Neurosurgery, Mayo Clinic, Mayo Medical School, Rochester, Minnesota.
J Neurosurg 1989 Apr;70(4):536-44 Abstract quote The records of 34 patients over 16 years of age with cerebellar medulloblastoma were retrospectively reviewed. All patients were treated by surgery, and all surviving patients were given radiation therapy.
The imaging characteristics of this rare entity were evaluated with regard to the tumor location in the cerebellum, and the prognostic effects of histological characteristics such as neuronal or glial differentiation and the presence of desmoplasia were investigated. Neither histological parameters nor tumor location (median, paramedian, or lateral cerebellar) affected patient survival. The desmoplastic variant was encountered in 38% of these adult medulloblastomas and occurred in all three cerebellar locations. The degree of surgical resection did not have a major effect on long-term survival; long-term survival was possible even in patients who had received only a biopsy.
The extent of initial radiation therapy was positively correlated with recurrence-free survival; full neuraxis irradiation was associated with a 13% incidence of delayed spinal metastases, whereas 75% of patients treated with irradiation of only the posterior fossa and/or the whole brain developed spinal deposits. A similar local recurrence rate (12.5%) was noted in both irradiation groups. Chemotherapy resulted in palliation in some patients with metastatic disease.
Cerebellar medulloblastomas in adults.Tekkok IH, Suzer T, Ozgen T, Erbengi A.
Department of Neurosurgery, Hacettepe University School of Medicine, Ankara, Turkey.
Neurosurg Rev 1991;14(2):135-40 Abstract quote A retrospective analysis of 32 patients older than 16 years of age treated at Neurosurgical Department of Hacettepe University within the last 30 years (1959-1988) for cerebellar medulloblastoma was considered. The clinical features, treatment modalities and outcome are discussed.
The survival rates for 5 and 10 years were 14% and 7% respectively. The results are compared with that of literature.
Medulloblastoma in late adults. Case report and critical review of the literature.Salvati M, Cervoni L.
Department of Neurosurgery, Mediterranean Neurological Neuromed Institute IRCCS, Pozzilli, Isernia, Italy.
J Neurosurg Sci 2000 Dec;44(4):230-2; discussion 232-3 Abstract quote BACKGROUND: Medulloblastoma in late adults (older than 65 years) is an exceptional occurrence; in fact only 8 cases are reported with complete clinical notes in the literature.
METHODS: The authors describe a case of medulloblastoma occurring in a 68-year-old man and analyzed cases reported in the literature.
RESULTS: The overall average age of the patients was 72.8 years (range 67-88 years), and the male prevalence of this tumour (70% of cases) seems to be unrelated to age. There is a lateral predominance in late adults (77.7% of cases). Seven patients underwent operation and subsequently these patients underwent a course of radiation therapy. Only two patient was treated with postoperative chemotherapy. Median survival for seven patients treated was 43.2 months (range 23-96 months).
CONCLUSIONS: It is interesting to note that: 1) histological analysis revealed a classic type medulloblastoma (88.8% of cases) similar to the children: 2) site of the tumor is lateral similar to the adults (77.7% of cases).
CONGENITAL
Congenital cerebellar medulloblastoma.Kim JH, Duncan C, Manuelidis EE.
Surg Neurol 1985 Jan;23(1):75-81 Abstract quote Congenital cerebellar medulloblastoma is extremely rare. Reported here is a female infant who presented her first abnormal clinical manifestations on the sixth day of life and who was subsequently found to have medulloblastoma at operation.
Electron microscopy revealed glial filaments and short cytoplasmic projections in some neoplastic cells and the presence of junctional complexes between neoplastic cells with and without glial filaments, which suggests the astrocytic differentiation of the tumor.
Including our own case, there have been only 21 reported cases of congenital cerebellar medulloblastoma. A strong female preponderance and some familial occurrence are noted in congenital cerebellar medulloblastoma.
DIRECT INVASION
Direct spread of medulloblastoma in adjacent extrameningeal tissues.Jamjoom ZB, el Saghir NS, Sadiq S, Malabarey T, al-Khudairy NN.
Division of Neurosurgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Acta Neurochir (Wien) 1989;97(3-4):171-6 Abstract quote A case of a medulloblastoma with extensive intradural dissemination and direct tumour spread from a lumbosacral deposit in the pelvis is presented. A review of the literature revealed six similar cases. In all of them direct invasion of contiguous structures occurred at sites of secondary deposits.
Two predilection site were identified: 1. The anterior fossa with tumour invasion of the paranasal air sinuses. 2. The lumbosacral spine with tumour extension into the retroperitoneum and pelvis. Generally, this unusual mode of tumour spread indicates a final stage in the course of the disease. The possible pathogenesis is discussed.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Cytologic findings of medulloblastoma in crush smears.Kumar PV, Hosseinzadeh M, Bedayat GR.
Department of Pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Iran.
Acta Cytol 2001 Jul-Aug;45(4):542-6 Abstract quote OBJECTIVE: To describe the cytologic findings of medulloblastomas on intraoperative crush preparation smears and compare them with the findings of other central nervous system tumors.
STUDY DESIGN: The intraoperative crush preparation smears of 19 cases of medulloblastoma were studied (6 undifferentiated type and 13 well-differentiated type). The findings were compared with those of a control group consisting of 31 astrocytomas, 22 ependymomas, 18 oligodendrogliomas, 27 meningiomas, 17 schwannomas, 17 pituitary adenomas, 3 lymphomas, 5 hemangioblastomas, 5 chordomas and 11 metastatic tumors.
RESULTS: Medulloblastomas revealed clusters and isolated small, round malignant cells with hyperchromatic nuclei and indistinct cytoplasm. Typical Homer-Wright rosettes were seen in the well-differentiated type, but they were poorly formed in the undifferentiated type. Tumor cannibalism, target inclusions, cytoplasmic vacuoles and prominent multiple nucleoli were noticed frequently in the undifferentiated type. The control group (metastatic tumors and high grade astrocytomas) rarely showed tumor cannibalism or multiple nucleoli.
CONCLUSION: Smears of the undifferentiated type of medulloblastomas frequently revealed tumor cannibalism, cytoplasmic vacuoles, target inclusions and prominent multiple nucleoli. These findings have been rarely reported. The prognosis of the undifferentiated type of medulloblastoma was poor.
Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study.Eberhart CG, Kepner JL, Goldthwaite PT, Kun LE, Duffner PK, Friedman HS, Strother DR, Burger PC.
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Cancer 2002 Jan 15;94(2):552-60 Abstract quote BACKGROUND: Medulloblastomas are small cell embryonal tumors of the cerebellum found predominantly in children, only slightly more than half of whom survive. Predicting favorable outcome has been difficult, and improved stratification clearly is required to avoid both undertreatment and overtreatment. Patients currently are staged clinically, but no pathologic staging system is in use. Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcome for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia. Therefore, the authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results.
METHODS: Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan-Meier and log-rank analyses.
RESULTS: Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival.
CONCLUSIONS: Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility.
VARIANTS LIPOMEDULLOBLASTOMA
Lipomatous medulloblastoma in adults. A distinct clinicopathological entity.Soylemezoglu F, Soffer D, Onol B, Schwechheimer K, Kleihues P.
Institute of Neuropathology, Department of Pathology, University Hospital, Zurich, Switzerland.
Am J Surg Pathol 1996 Apr;20(4):413-8 Abstract quote We report on three patients who presented with a cerebellar medulloblastoma at age 48, 53, and 59 years.
Histopathology showed typical features of medulloblastoma, in one case with marked neuronal differentiation. In addition, all neoplasms contained focal accumulations of mature fat cells. Immunoreactivity of adipocytes for S-100 protein, neuron-specific enolase, synaptophysin, microtubule-associated protein-2, and glial fibrillary acidic protein and the lack of immunoreactivity to type IV collagen suggest lipomatous differentiation of neoplastic primitive neuroectodermal cells rather than an admixture of mesenchymal elements. Mitotic activity was low and the growth faction, as determined by the MIB-1 labeling index, was less than 5%. All patients are alive with a recurrence-free interval ranging from 3.5 to 12 years.
These three patients and five similar previously reported cases all fit into the concept of the lipomatous medulloblastoma as a new clinicopathological entity characterized by (a) typical features of a cerebellar medulloblastoma with advanced neuronal differentiation, (b) areas of lipomatous differentiation, (c) low proliferative potential, (d) manifestation in adults (mean age, 50 years), and (e) apparent favorable clinical prognosis.
Lipomedulloblastoma in a child: a controversial entity.
Sharma MC, Agarwal M, Suri A, Gaikwad S, Mukhopadhyay P, Sarkar C.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Hum Pathol 2002 May;33(5):564-9 Abstract quote Lipomedulloblastoma is regarded as a distinct entity that occurs exclusively in adults and has a low proliferative potential and a favorable outcome.
We describe a rare case of lipomedulloblastoma in a 6-year-old female child showing a high labeling index that needs documentation. The various hypotheses of adiposal change are discussed.
MEDULLOMYOBLASTOMA
Medullomyoblastoma. A case report.Lata M, Mahapatra AK, Sarkar C, Roy S.
Indian J Cancer 1989 Dec;26(4):240-6 Abstract quote A case of medullomyoblastoma was studied by light and electron microscopy and by immunohistochemistry. It showed glial and neuronal differentiation in the medulloblastoma areas and rhabdomyoblastic differentiation in the intervening areas
Medullomyoblastoma: case report.Cheema ZF, Cannon TC, Leech R, Brennan J, Adesina A, Brumback RA.
Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USA
J Child Neurol 2001 Aug;16(8):598-9 Abstract quote This 7-year-old boy presented with a 2-week history of headache, nausea, vomiting, anorexia, lethargy, and unsteadiness of gait. Brain magnetic resonance imaging (MRI) revealed a cystic mass within the vermis of the cerebellum.
A suboccipital craniectomy was performed to remove a tumor that contained primitive neuroectodermal cells with florid skeletal muscle differentiation. Immunohistochemical studies and electron microscopy confirmed the presence of both a primitive neuroectodermal component and rhabdomyoblastic differentiation, consistent with the diagnosis of medullomyoblastoma.
This exceedingly rare tumor of the cerebellar vermis of children is characterized by two components: primitive neuroectodermal tumor cells and skeletal muscle. Although the histogenesis remains uncertain, advances in immunohistochemistry and electron microscopy suggest the origin of this tumor from a multipotential stem cell precursor.
SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE
Apoptosis, neuronal maturation, and neurotrophin expression within medulloblastoma nodules.Eberhart CG, Kaufman WE, Tihan T, Burger PC.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Neuropathol Exp Neurol 2001 May;60(5):462-9 Abstract quote Nodular/desmoplastic medulloblastomas are a well-established histopathological subtype containing reticulin-free nodules or "pale islands' that are comprised of cells with round "neurocytic" nuclei and abundant cytoplasm. Significant neuronal maturation occurs within nodules.
We used immunohistochemistry to evaluate neuronal differentiation in the nodules of 6 of these tumors. The neuronal markers NeuN, synaptophysin, and MAP-2 were identified in the "pale islands" of all 6 nodular medulloblastomas examined, and high and medium molecular weight nonphosphorylated neurofilaments were detected in 2 of the 6 cases. We also observed collections of apoptotic cells within nodules. Given the known role of neurotrophin signaling in neuronal maturation and apoptosis, we analyzed immunohistochemically the distribution of neurotrophin receptors TrkA and TrkC and their primary ligands NGF and NT3 in 14 nodular medulloblastomas. TrkA and TrkC were detected in 13 and 10 cases, respectively, and were predominantly localized within nodules. NGF and NT3 were distributed diffusely with some nodular accentuation. The localized expression of Trk receptors within nodules of desmoplastic medulloblastomas suggests neurotrophin signaling is involved in the apoptosis and neuronal differentiation in medulloblastomas. We also examined expression of p53 and BCL-2 in these tumors; both were prominent in internodular regions but only weakly expressed within nodules. Trk receptors, p53, and BCL-2 are all expressed during development of the normal cerebellum. Interestingly, the immunohistochemical expression profile of these proteins in the differentiating nodules of medulloblastomas is in many ways similar to their expression in the developing cerebellum.
Thus similar signaling pathways may be operational in cerebellar development and medulloblastoma tumor differentiation.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES MALIGNANT RHABDOID TUMOR
Congenital disseminated malignant rhabdoid tumor and cerebellar tumor mimicking medulloblastoma in monozygotic twins: pathologic and molecular diagnosis.Fernandez C, Bouvier C, Sevenet N, Liprandi A, Coze C, Lena G, Figarella-Branger D.
Service d'Anatomie Pathologique et de Neuropathologie, CHU Timone, 264 rue Saint-Pierre, 13385 Marseille cedex 05, France.
Am J Surg Pathol 2002 Feb;26(2):266-70 Abstract quote Malignant rhabdoid tumors are highly aggressive childhood tumors. Recently, all of the malignant rhabdoid tumors, whatever their location, have been related to the inactivation of the hSNF5/INI1 gene. A subset of cerebral tumors, associated with malignant rhabdoid tumors or isolated ones arising in siblings, showed similar molecular alterations.
We report for the first time in monozygotic twins a congenital disseminated malignant rhabdoid tumor in one twin and a cerebellar tumor mimicking a medulloblastoma in the other. Molecular analysis revealed similar alterations for both tumors: a deletion of exon 7 of the hSNF5/INI1 gene in one allele, and a point mutation in the same exon in the other, suggesting a common genetic pathway. Analysis of constitutional DNA revealed a germline mutation.
These findings are in favor of a common etiology for rhabdoid tumor and a subset of brain tumors developing in infancy.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
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