Original ArticlesALK-positive Histiocytosis of the Breast A Clinicopathologic Study Highlighting Spindle Cell HistologyKashima, Jumpei MD*,†; Yoshida, Masayuki MD, PhD*; Jimbo, Kenjiro MD, PhD‡; Izutsu, Koji MD, PhD§,∥; Ushiku, Tetsuo MD, PhD†; Yonemori, Kan MD, PhD∥,¶; Yoshida, Akihiko MD, PhD*,∥ Author Information Departments of *Diagnostic Pathology ‡Breast Surgery §Hematology ¶Breast and Medical Oncology ∥Rare Cancer Center, National Cancer Center Hospital †Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Conflicts of Interest and Source of Funding: Supported in part by JSPS Grant-in-Aid for Young Scientists 18K15108 (A.Y.). K.I. received research grants and honoraria from Chugai Pharmaceutical Co. Ltd that are not related to this study. K.Y. served as an advisor for Chugai Pharmaceutical Co. Ltd, but not related to this study. For the remaining authors none were declared. Correspondence: Akihiko Yoshida, MD, PhD, Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (e-mail: [email protected]). The American Journal of Surgical Pathology: March 2021 - Volume 45 - Issue 3 - p 347-355 doi: 10.1097/PAS.0000000000001567 Buy SDC Metrics Abstract Originally described as a systemic self-limiting disease in infancy, the spectrum of ALK-positive histiocytosis has recently been broadened to include localized diseases in older children and young adults. Despite different manifestations, these tumors share histologic characteristics and a highly recurrent KIF5B-ALK fusion. ALK-positive histiocytosis is poorly characterized in the breast. In this study, we report 3 cases of ALK-positive histiocytosis of the breast. The patients were Asian women, aged 16 to 45 years. Two patients presented with an isolated breast mass, while 1 exhibited multiorgan involvement. The latter patient received ALK inhibitor after surgery, which led to complete remission. Histologically, well-circumscribed tumors displayed fascicular and storiform growth of uniform, nonatypical spindle cells admixed with lymphocytic infiltrates. Fewer conventional epithelioid histiocytes with lobulated or clefted nuclei were observed within the same breast tumors in 2 cases or within a concomitant brain tumor in the third case. Touton-type giant cells were focally present in 2 cases. Immunohistochemically, tumor spindle, and epithelioid cells were diffusely positive for CD163 and ALK in all cases and focally positive for S100 protein in 1 of the cases. CD1a and langerin were negative. Actin-positive myofibroblasts were admixed within the tumor in 2 cases, and their reactive nature was highlighted using double immunostaining. Break-apart fluorescence in situ hybridization assay demonstrated gene rearrangements involving KIF5B and ALK in all the 3 cases. ALK-positive histiocytosis rarely occurs as a spindle cell breast tumor, and should be distinguished from other diseases such as inflammatory myofibroblastic tumors and spindled histiocytic reaction. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.