Akihiko Yoshida1,2, Yasuhito Arai3, Natsuko Hama3, Hiroshi Chikuta3, Yoshimi Bando4, Seiichi Nakano5, Eisuke Kobayashi2,6, Junji Shibahara7, Hiroshi Fukuhara8, Motokiyo Komiyama2,9, Shun-Ichi Watanabe10, Kenji Tamura11, Akira Kawai2,6, Tatsuhiro Shibata3. 1. Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan. 2. Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan. 3. Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan. 4. Division of Pathology, Tokushima University Hospital, Tokushima, Japan. 5. Department of Otolaryngology, Tokushima University Graduate School of biomedical Sciences, Tokushima, Japan. 6. Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan. 7. Department of Pathology, Faculty of Medicine, Kyorin University, Tokyo, Japan. 8. Department of Urology, Faculty of Medicine, Kyorin University, Tokyo, Japan. 9. Department of Urology, National Cancer Center Hospital, Tokyo, Japan. 10. Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. 11. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Abstract
AIMS: BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR-associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied seven cases of BCOR-associated non-uterine sarcomas in adult patients. METHODS AND RESULTS: The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR-CCNB3. One tumor with a ZC3H7B-BCOR occurred in the chest wall, and a tumor with a novel CIITA-BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR-CCNB3 sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B-BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA-BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non-myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR-CCNB3 sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization. CONCLUSIONS: This study expands the clinicopathologic and molecular spectrum of BCOR-associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non-uterine sarcomas.
AIMS: BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR-associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied seven cases of BCOR-associated non-uterine sarcomas in adult patients. METHODS AND RESULTS: The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR-CCNB3. One tumor with a ZC3H7B-BCOR occurred in the chest wall, and a tumor with a novel CIITA-BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR-CCNB3sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B-BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA-BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non-myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR-CCNB3sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization. CONCLUSIONS: This study expands the clinicopathologic and molecular spectrum of BCOR-associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non-uterine sarcomas.
Authors: Florencia Cidre-Aranaz; Sarah Watson; James F Amatruda; Takuro Nakamura; Olivier Delattre; Enrique de Alava; Uta Dirksen; Thomas G P Grünewald Journal: Nat Rev Dis Primers Date: 2022-10-06 Impact factor: 65.038
Authors: Andres M Acosta; Lynette M Sholl; Brendan C Dickson; Jesse K McKenney; Jennifer B Gordetsky; Michael R Pins; Adrian Marino-Enriquez; Fei Dong; Adrian M Dubuc; Paola Dal Cin; Christopher D M Fletcher Journal: Mod Pathol Date: 2021-05-13 Impact factor: 7.842
Authors: David J Pisapia; Kentaro Ohara; Rohan Bareja; David C Wilkes; Erika Hissong; Jaclyn A Croyle; Joon-Hyung Kim; Jad Saab; Theresa Y MacDonald; Shaham Beg; Catherine O'Reilly; Sarah Kudman; Mark A Rubin; Olivier Elemento; Andrea Sboner; Jeffrey Greenfield; Juan Miguel Mosquera Journal: Acta Neuropathol Commun Date: 2020-06-03 Impact factor: 7.801