Original ArticlesCNS Low-grade Diffusely Infiltrative Tumors With INI1 Deficiency, Possessing a High Propensity to Progress to Secondary INI1-deficient Rhabdoid TumorsNobusawa, Sumihito MD*; Nakata, Satoshi MD†; Nakano, Yoshiko MD‡; Kawamura, Atsufumi MD§; Yoshida, Makiko MD∥; Tamura, Akihiro MD¶; Hasegawa, Daiichiro MD¶; Kosaka, Yoshiyuki MD¶; Ito, Ichiro MD#; Watanabe, Reiko MD**; Oishi, Takuma MD††; Hayashi, Nakamasa MD‡‡; Ishikawa, Eiichi MD§§; Sakamoto, Noriaki MD∥∥; Okura, Naoki MD¶¶; Murakami, Chiaki MD*; Ichimura, Koichi MD‡; Hirato, Junko MD##; Yokoo, Hideaki MD*Author Information *Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi ‡Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo Departments of §Neurosurgery ∥Pathology ¶Hematology and Oncology, Hyogo Prefectural Kobe Children’s Hospital, Kobe #Department of Pathology, Nagano Red Cross Hospital, Nagano **Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa ††Division of Pathology ‡‡Division of Neurosurgery, Shizuoka Cancer Center, Nagaizumi Departments of §§Neurosurgery ∥∥Diagnostic Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba ¶¶Department of Radiology, International University of Health and Welfare, School of Medicine, Narita ##Department of Pathology, Public Tomioka General Hospital, Tomioka, Japan †Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Sumihito Nobusawa, MD, Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi 371-8511, Gunma Prefecture, Japan (e-mail: email@example.com). The American Journal of Surgical Pathology: November 2020 - Volume 44 - Issue 11 - p 1459-1468 doi: 10.1097/PAS.0000000000001520 Buy Metrics Abstract Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant tumors of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (rarely) BRG1. Most AT/RT are identified as primary tumors; however, rare AT/RT or INI1-deficient RTs arising from other primary tumors have been reported. Here, we report 3 cases of hitherto unclassifiable low-grade tumors with loss of INI1 nuclear expression, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1), 2 of which progressed to secondary RT. All 3 CNS LGDIT-INI1 exhibited a similar histology: diffusely distributed small tumor cells with round to oval or irregular nuclei and scant cytoplasm were admixed with degenerative neurons and large reactive astrocytes in an edematous, myxoid, or collagenous background. Mitotic figures were absent. Immunohistochemistry revealed that the tumor cells in all 3 CNS LGDIT-INI1 and 2 RT were negative for INI1. Genetically, total or partial homozygous deletions of the INI1 gene were detected in all CNS LGDIT-INI1 and RT excluding 1 CNS LGDIT-INI1 without sufficient DNA quality and quantity. Despite the loss of INI1 expression, these low-grade lesions were clearly distinguishable from AT/RT by their low proliferative activity, diffusely infiltrative growth pattern, and lack of rhabdoid cells and polyphenotypic immunoreactivity. In conclusion, CNS LGDIT-INI1 may represent a rare group of tumors that are clinically indolent but have a high propensity to progress to RT. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.