Contributed by Takahiro Aoki, MD, Hiroshi Kishimoto, MD, Junko Hirato, MD, PhD, Yonehiro Kanemura, MD, PhD, Makiko Mori, MD, Yuki Arakawa, MD, Jun Kurihara, MD, Eiji Oguma, MD, Katsuyoshi Koh, MD
FINAL DIAGNOSIS
Anaplastic Medulloblastoma with Rhabdoid Features
DISCUSSION
A malignant central nervous system (CNS) embryonal tumor with poorly differentiated cells, including rhabdoid cells, in pediatric patients is usually an atypical teratoid/rhabdoid tumor (AT/RT); however, the tumor cells in this patient were positive for both INI1 and BRG1, which are inactive in an AT/RT. There is another entity of CNS embryonal tumor with rhabdoid features in the 2016 WHO Revised Classification of Tumors of the CNS (3); however, the tumor cells revealed poor polyphenotypic differentiation and were positive for desmin. These findings make the tumor incompatible with this entity. In addition, because the rhabdoid cells in this tumor demonstrated neural differentiation as well as the other lesion in the tumor, we diagnosed the tumor as an anaplastic medulloblastoma with rhabdoid features, which is referred to as a composite rhabdoid tumor. There is a similar case report of a metastatic medulloblastoma with focal rhabdoid differentiation, which also showed anaplastic features and was positive for INI1, synaptophysin, and desmin (2).
Perry et al. (4) suggested an entity of rhabdoid tumor called composite rhabdoid tumor, which is a secondary morphologic phenotype, typically signifying the emergence of cytologic anaplasia. Most rhabdoid tumors are diagnosed in adult patients, and the retention of INI1 expression is specific for distinguishing a malignant rhabdoid tumor and AT/RT from a composite rhabdoid tumor. A pediatric composite rhabdoid tumor is extremely rare; however, this case was compatible with a composite rhabdoid tumor and not an AT/RT or CNS embryonal tumor with rhabdoid features because of the following three points: 1) retention of INI1 and BRG1, 2) poor polyphenotypic differentiation, and 3) anaplastic findings in the tumor. The clinically poor prognosis in this case was also consistent with the finding in the report by Perry et al.
Genetic analysis using gene expression profiling and Sanger sequencing (1) revealed sonic hedgehog (SHH) activation and TP53 mutation. A medulloblastoma with SHH activation and TP53 mutation often shows large cell/anaplastic morphology, and the clinical outcome is very poor (1, 5). The relationship between SHH activation or TP53 mutation and a composite rhabdoid tumor has not been elucidated to date. Tumors with TP53 mutation often show poor prognosis; however, TP53 mutation is not very rare in an SHH-activated medulloblastoma when compared with a composite rhabdoid tumor. Further research to clarify the etiology of development of a composite rhabdoid tumor is needed to treat this poor prognostic subgroup.
REFERENCES
ACKNOWLEDGMENTS
The authors thank Dr. Atsuko Nakazawa at National Center for Child Health and Development for staining BRG1 and Japan Children's Cancer Group for providing a central diagnostic service supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development, AMED.
Contributed by Takahiro Aoki, MD, Hiroshi Kishimoto, MD, Junko Hirato, MD, PhD, Yonehiro Kanemura, MD, PhD, Makiko Mori, MD, Yuki Arakawa, MD, Jun Kurihara, MD, Eiji Oguma, MD, Katsuyoshi Koh, MD
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