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Large cell/anaplastic medulloblastoma: Outcome according to myc status, histopathological, and clinical risk factors
Author(s) -
von Hoff Katja,
Hartmann Wolfgang,
von Bueren André Oscar,
Gerber Nicolas Ulrich,
Grotzer Michael Andreas,
Pietsch Torsten,
Rutkowski Stefan
Publication year - 2010
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22339
Subject(s) - medulloblastoma , medicine , histology , anaplasia , large cell , oncology , pathology , cancer , adenocarcinoma
Purpose 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%). Conclusion 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. Pediatr Blood Cancer 2010;54:369–376. © 2009 Wiley‐Liss, Inc.