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Clinical Trial
. 2011 Aug;135(8):984-93.
doi: 10.5858/2010-0515-OAR1.

Embryonal central nervous system neoplasms arising in infants and young children: a pediatric brain tumor consortium study

Roger E McLendon  1 , Adesina Adekunle, Veena Rajaram, Mehmet Koçak, Susan M Blaney
Affiliations
Clinical Trial

Embryonal central nervous system neoplasms arising in infants and young children: a pediatric brain tumor consortium study

Roger E McLendon et al. Arch Pathol Lab Med. 2011 Aug.

Abstract

Context: Medulloblastomas (MBs) and atypical teratoid/rhabdoid tumors (AT/RTs) arising in infants and children can be difficult to distinguish; however, histologic characterization is prognostically important.

Objective: To determine histologic and phenotypic markers associated with utility with progression-free survival (PFS) and overall survival (OS) in children younger than 3 years with MBs and AT/RTs.

Design: We undertook a histologic and immunophenotypic study of MBs and AT/RTs arising in infants and children younger than 3 years treated in a Pediatric Brain Tumor Consortium study. The 41 girls and 55 boys ranged in age from 2 to 36 months at enrollment. These infants and children exhibited 51 MBs, 26 AT/RTs, and 24 other tumors (not further studied). Median follow-up of the patients was 17.2 months from diagnosis (range: 1.4-93 months).

Results: Infants and children with AT/RT exhibited a statistically significant shorter PFS and OS when compared to infants and children with MBs (both P < .001). A lack of nuclear BAF47 immunohistochemical reactivity proved reliable in identifying AT/RTs. Among MBs, our data suggest an association of nodularity and prolonged PFS and OS, which must be independently confirmed. Anaplasia correlated with OTX2 reactivity and both OTX2 and moderate to severe anaplasia correlated with PFS but not with OS.

Conclusion: Distinguishing AT/RT from MBs is clinically important. For expert neuropathologists, the diagnoses of AT/RT and MB can be reliably made from hematoxylin-eosin stains in the vast majority of cases. However certain rare small cell variants of AT/RT can be confused with MB. We also found that immunohistochemical reactivity for BAF47 is clinically useful in distinguishing MBs from AT/RTs and for identifying certain small cell AT/RTs. Among MBs, nodularity may be an important prognostic factor for improved PFS and OS in infants and children.

Trial registration: ClinicalTrials.gov NCT00042367.

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Figures

Figure 1
Figure 1
A. Epithelioid features and large, round, open nuclei with prominent nucleoli are features of the AT/RT. B, Scattered islands of immunoreactivity without obvious differentiation are also found (A:H&E; 40x; B:Glial fibrillary acidic protein, 40X).
Figure 2
Figure 2
A, Nodular MBs often demonstrate pale islands of tumor cells surrounded by smaller, more densely compacted regions of tumor cells. B, The pale islands frequently are outlined by strands of reticulin that surround the smaller cell population (A: H&E, 10X; B: Wilder's reticulin, 20X).
Figure 3
Figure 3
Some tumors that exhibit pericellular reticulin lack the pale islands. Despite the presence of diffuse pericellular reticulin, confusingly, these tumors are not considered “desmoplastic” by the WHO, a designation reserved for the nodular tumors (Wilder's reticulin; 40X).
Figure 4
Figure 4
Large cell MBs exhibit large, round nuclei with prominent nucleoli. They are distinguished from AT/RTs by their minimal cytoplasm and frequent association with anaplastic change (H&E; 60X).
Figure 5
Figure 5
Severely anaplastic MB with dark, pleomorphic nuclei overlapping adjacent tumor cells. Severely anaplastic MB with frequent apoptotic nuclei and geographic necrosis. Moderately anaplastic MB with starry sky apoptosis. Mildly anaplastic MB with hyperchromatic nuclei and rare apoptotic cells (a, H&E; 40X; B, H&E 40X; C, H&E, 20X; D. H&E, 20X).
Figure 6
Figure 6
A, Progression-free survival estimates by degrees of anaplasia (MB patients). B, Overall survival by degrees of anaplasia (MB patients).
Figure 7
Figure 7
A, Progression-free survival estimates by degrees of nodularity (MB patients). B, Overall survival by degrees of nodularity (MB patients).
Figure 8
Figure 8
A, Tumor from patient 60775 reveals no epithelioid or rhabdoid features by H&E. B, Negative BAF47 reactivity is noted in the tumor with intact endothelial cell immunoreactivity (a, H&E, 40X; B, anti-BAF47, 40X)
Figure 9
Figure 9
A, Tumor from patient 107487 diagnosed by institution as AT/RT. B, Diffuse BAF47 immunoreactivity present (A, H&E, 40X; B, BAF47, 40X)
Figure 10
Figure 10
Overall (P<0.001) and Progression-free survival (P<0.001) estimates by diagnostic category. (MB versus ATRT).
See this image and copyright information in PMC

References

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