Original ArticlesThoracic SMARCA2-deficient But SMARCA4-preserved Tumors With Undifferentiated Morphology Combined With Claudin-4 NegativityIwakoshi, Akari MD, PhD*; Sasaki, Eiichi MD, PhD†; Sato, Mariko MD‡; Sugiyama, Keiji MD‡; Kogure, Yoshihito MD, PhD‡,§; Kitagawa, Chiyoe MD, PhD‡,§; Nishimura, Rieko MD, PhD* Author Information Departments of *Pathology ‡Medical Oncology §Respiratory Medicine, National Hospital Organization Nagoya Medical Center †Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Aichi Prefecture, Japan A.I. and E.S.: conceived and designed the study; generated tables and figures. A.I., M.S., K.S., Y.K., C.K., and R.N.: contributed to the materials and patients. A.I., E.S., and R.N.: provided a pathology review and wrote the paper. Conflicts of Interest and Source of Funding: Supported by Nagoya Medical Center. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Eiichi Sasaki, MD, PhD, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Aichi Prefecture, Japan (e-mail: [email protected]). The American Journal of Surgical Pathology: July 2022 - Volume 46 - Issue 7 - p 1000-1006 doi: 10.1097/PAS.0000000000001879 Buy Metrics Abstract Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized tumor characterized by inactivation of SMARCA4, a SWItch/Sucrose NonFermentable chromatin remodeler, detectable by immunohistochemistry. SMARCA4-UT shows undifferentiated or rhabdoid morphology with claudin-4 negativity. However, thoracic undifferentiated tumors with the same histologic features as SMARCA4-UTs but a preserved SMARCA4 expression have so far been underrecognized. We herein report 3 cases of thoracic undifferentiated tumors with isolated loss of SMARCA2 but retained expression of SMARCA4 and SMARCB1. The present tumors were found in 2 men and 1 woman, 40 to 50 years old. All patients were heavy smokers (≥20 pack-years). The tumors were generally large masses located in the mediastinum, lung>chest wall, or lung and composed of relatively monotonous, round to epithelioid cells with variably rhabdoid cells. Immunohistochemically, the tumors showed claudin-4 negativity with variable expression of cytokeratin. All cases showed highly aggressive clinical behavior with overall survival of 2 to 10 months. These SMARCA2-deficient tumors with preserved SMARCA4 expression appeared to be clinicopathologically indistinguishable from SMARCA4-UTs, except for in their SMARCA4 status. This variant may expand the spectrum of SWItch/Sucrose NonFermentable–deficient undifferentiated tumors of the thoracic region beyond SMARCA4-UT. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.