Large cell/anaplastic medulloblastoma: outcome according to myc status, histopathological, and clinical risk factors.
OBJECTIVE
To evaluate the prognostic impact of large cell/anaplastic (LC/A) histology together with molecular and clinical risk factors in childhood medulloblastoma.


METHODS
Three consecutive prospective medulloblastoma trials were screened for patients with the histological diagnosis of LC/A medulloblastoma. Tumors were considered as LC/A if they displayed areas of severe cytological anaplasia or a significant or predominant large cell component. Histology was centrally confirmed. Genomic DNA amplification of c-myc and n-myc, and mRNA expression of c-myc and trkC were analyzed.


RESULTS
Twenty-eight patients with LC/A medulloblastoma with a median age of 6.1 years (1.4-16.5 years) and a median follow-up of 4.5 years were identified (5% of all medulloblastoma). Four-year event-free (EFS) and overall survival (OS) were 58% and 67%. Young age and metastases (n = 13, 4-year EFS 31% vs. 82% in 15 children >4 years and without metastases, P = 0.001), large cell histology (n = 9, 4-year EFS 22% vs. 75%, P = 0.005) and c-myc amplification (n = 9, 4-year EFS 22% vs. 89%, P < 0.0001) were negative prognostic factors. C-myc amplification was highly correlated with young age (P < 0.001), metastases (P = 0.002) and large cell histology (P = 0.007). Outcome of 12 patients with severely anaplastic tumors without these risk factors was not impaired (4-year EFS 86%).


CONCLUSIONS
In a subgroup of patients without clinical and molecular risk factors outcome was favorable despite severely anaplastic histology. In contrast, c-myc amplification and large-cell histology were associated with an inferior outcome. Intensified treatment strategies should be considered for children with LC/A medulloblastoma and these characteristics.
von Hoff
Katja
K
Department of Pediatrics, University of Wuerzburg, Wuerzburg, Germany.
Hartmann
Wolfgang
W
von Bueren
André Oscar
AO
Gerber
Nicolas Ulrich
NU
Grotzer
Michael Andreas
MA
Pietsch
Torsten
T
Rutkowski
Stefan
S
D000293:Adolescent; D000367:Age Factors; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020812:Receptor, trkC / Q000096:biosynthesis / Q000235:genetics; D012307:Risk Factors
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D020812:Receptor, trkC