Secondary INI1-deficient rhabdoid tumors of the central nervous system: analysis of four cases and literature review

  • Sumihito NobusawaEmail author
  • Satoshi Nakata
  • Yuka Yoshida
  • Tatsuya Yamazaki
  • Keisuke Ueki
  • Keishiro Amano
  • Junkoh Yamamoto
  • Makiko Miyahara
  • Tsutomu Sugai
  • Yoichi Nakazato
  • Junko Hirato
  • Hideaki Yokoo
Original Article


Atypical teratoid/rhabdoid tumors (AT/RT) are rare, highly malignant neoplasms of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (extremely rarely) BRG1. The vast majority of AT/RT are recognized as primary tumors; however, rare AT/RT or INI1-deficient RT arising from other primary tumors have been reported. To better characterize secondary RT, we performed a histological and molecular analysis of four RT arising from pleomorphic xanthoastrocytoma (PXA), anaplastic PXA, low-grade astrocytoma, or ependymoma. Histologically, although conventional AT/RT are usually not largely composed of rhabdoid cells, three secondary RT were composed mainly of rhabdoid cells, two of which arising from (anaplastic) PXA exhibited marked nuclear pleomorphism reminiscent of that in the precursor lesions. Regarding INI1 alterations, although mutations including small indels are frequent in conventional AT/RT, only in one secondary RT had a mutation. Moreover, together with previously reported cases, biallelic INI1 inactivation in secondary RT was mostly due to biallelic focal and/or broad deletions. Although conventional AT/RT have stable chromosomal profiles, i.e., the frequency of copy number changes involving chromosomes other than chromosome 22 is remarkably low, our array comparative genomic hybridization analysis revealed numerous copy number changes in the secondary RT. In conclusion, secondary RT of the central nervous system are clinicopathologically and molecularly different from conventional pediatric AT/RT, and a nosological issue is whether these secondary RT should be called secondary “AT/RT” as most of the reported cases were.


AT/RT INI1 SMARCB1 Rhabdoid cells 



We thank Ms. Machiko Yokota (Gunma University) for her excellent technical assistance.

Author contributions

S. Nobusawa conceived and designed the experiments; S. Nobusawa, Y.N., J.H, and H.Y. performed the pathological analysis; S. Nobusawa, T.Y., and K.U. performed the laboratory research; K.A., J.Y., M.M., and T.S. performed patient management; S. Nobusawa, S. Nakata, and Y.Y. analyzed and interpreted the data; S. Nobusawa, S. Nakata, and Y.Y. wrote the manuscript; Y.N, J.H, and H.Y. participated in construction of the manuscript and revised it critically; and all authors accepted the final version of the manuscript.

Compliance with ethical standards

The present study was approved by the Gunma University Ethical Committee.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2019_2686_MOESM1_ESM.xlsx (12 kb)
ESM 1 (XLSX 12 kb).
428_2019_2686_MOESM2_ESM.xlsx (14 kb)
ESM 2 (XLSX 14 kb).


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sumihito Nobusawa
    • 1
    Email author
  • Satoshi Nakata
    • 2
  • Yuka Yoshida
    • 1
  • Tatsuya Yamazaki
    • 1
  • Keisuke Ueki
    • 3
  • Keishiro Amano
    • 4
  • Junkoh Yamamoto
    • 5
  • Makiko Miyahara
    • 6
  • Tsutomu Sugai
    • 7
  • Yoichi Nakazato
    • 8
  • Junko Hirato
    • 1
    • 9
  • Hideaki Yokoo
    • 1
  1. 1.Department of Human PathologyGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of NeurosurgeryDokkyo Medical University HospitalMibuJapan
  4. 4.Department of PediatricsMie University Graduate School of MedicineTsuJapan
  5. 5.Department of NeurosurgeryUniversity of Occupational and Environmental HealthKitakyushuJapan
  6. 6.Department of NeurosurgeryNational Center for Global Health and MedicineTokyoJapan
  7. 7.Department of NeurosurgeryYamagata Prefectural Central HospitalYamagataJapan
  8. 8.Department of PathologyHidaka HospitalTakasakiJapan
  9. 9.Department of PathologyPublic Tomioka General HospitalTomiokaJapan

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