Original ArticlesCyclin D1 Is Expressed in Neoplastic Cells of Langerhans Cell Histiocytosis but Not Reactive Langerhans Cell ProliferationsShanmugam, Vignesh MD; Craig, Jeffrey W. MD, PhD; Hornick, Jason L. MD, PhD; Morgan, Elizabeth A. MD; Pinkus, Geraldine S. MD; Pozdnyakova, Olga MD, PhD Author Information Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 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: Olga Pozdnyakova, MD, PhD, Department of Pathology, Brigham and Women’s Hospital, Boston, MA 01772 (e-mail: [email protected]). The American Journal of Surgical Pathology: October 2017 - Volume 41 - Issue 10 - p 1390-1396 doi: 10.1097/PAS.0000000000000897 Buy Metrics Abstract Langerhans cell histiocytosis (LCH) is characterized by frequent activating mutations involving the mitogen-activated protein kinase (MAPK) pathway. Therefore, downstream markers of MAPK pathway activation such as cyclin D1 may be useful as novel diagnostic markers of neoplasia in LCH. The goal of this study was to investigate cyclin D1 expression in LCH and reactive Langerhans cell accumulations using immunohistochemistry on archival tissue. All LCH cases tested (39/39) showed cyclin D1 expression in CD1a/Langerin+ cells. Most cases (22/39; 56%) showed strong cyclin D1 expression in the majority (≥50%) of lesional cells. Only a few cases (6/39; 15%) showed cyclin D1 expression in a small subset (<20%). Nearly all LCH cases (26/27; 96%) showed p-ERK expression by immunohistochemistry, parallel to cyclin D1 expression. CD1a+ Langerhans cells in all cases of florid dermatopathic lymphadenopathy and normal skin were negative for cyclin D1, as demonstrated by CD1a/cyclin D1 double staining. The majority of skin specimens (14/18; 78%) with dermatitis-related changes did not show cyclin D1 expression in the CD1a+ epidermal Langerhans cell aggregates. A minority (4/18; 22%) showed weak cyclin D1 staining in a small subset (5% to 10%) of CD1a+ Langerhans cells. We conclude that cyclin D1 is ubiquitously expressed in LCH, in keeping with the known near universal MAPK activation in this disease. Further, it is not significantly expressed in reactive Langerhans cell proliferations in lymph node or skin. Therefore, cyclin D1 immunohistochemistry may be useful in excluding non-neoplastic mimics of LCH. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.