Original ArticlesJAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic MorphologyFitzpatrick, Megan J. MD*; Massoth, Lucas R. MD*; Marcus, Chelsea MD†; Vergilio, Jo-Anne MD†; Severson, Eric MD, PhD†; Duncan, Daniel MD†; Ramkissoon, Shakti H. MD, PhD†,‡; Hasserjian, Robert P. MD*; Kim, Annette S. MD, PhD§; Sohani, Aliyah R. MD*; Williams, Erik A. MD†,∥; Nardi, Valentina MD*Author Information *Department of Pathology, Massachusetts General Hospital, Harvard Medical School §Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston †Foundation Medicine Inc., Cambridge, MA ‡Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC ∥Department of Pathology, Department of Dermatology, UCSF Dermatopathology Service, University of California San Francisco, San Francisco, CA M.J.F. and L.R.M. contributed equally. E.A.W. and V.N. jointly supervised this study. Conflicts of Interest and Source of Funding: C.M., J.V., E.S., D.D., S.H.R., and E.A.W. are employees of Foundation Medicine Inc., a wholly owned subsidiary of Roche Holdings Inc. and Roche Finance Ltd, and have equity interest in an affiliate of these Roche entities. A.R.S. has served as an expert consultant in cases involving breast implant associated anaplastic large cell lymphoma for the law firms of Seeger Salvas & Devine LLP and Levin Papantonio PA, Arnold & Itkin LLP. A.S.K. serves as a consultant for LabCorp Inc. and has research funding from the Multiple Myeloma Research Foundation. For the remaining authors none were declared. Correspondence: Valentina Nardi, MD, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 820A, Boston, MA 02114 (e-mail: [email protected]). The American Journal of Surgical Pathology: July 2021 - Volume 45 - Issue 7 - p 895-904 doi: 10.1097/PAS.0000000000001708 Buy Metrics Abstract Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement. We describe a series of 6 JAK2 rearrangements occurring in a cohort of 97 CD30+ ALK− PTCL (6%), assembled after identifying an index case of a novel PABPC1-JAK2 fusion in a case of ALK− anaplastic large cell lymphoma with unusual classic Hodgkin lymphoma (CHL)-like features. Fusions were identified using a comprehensive next-generation sequencing based assay performed between 2013 and 2020. Five of 6 cases (83%) showed JAK2 rearrangements with 4 novel partners: TFG, PABPC1, ILF3, and MAP7, and 1 case demonstrated a previously described PCM1-JAK2 fusion. By morphology, all cases showed anaplastic large cells and multinucleated Reed-Sternberg–like cells within a polymorphous inflammatory background with frequent eosinophilia reminiscent of CHL. By immunohistochemistry, atypical large cells expressed CD30 with coexpression of at least 1 T-cell marker, aberrant loss of at least 1 T-cell marker and, in 4 of 5 cases stained (80%), unusual CD15 coexpression. These findings suggest that a subset of CD30+ ALK− systemic PTCL with anaplastic morphology carry JAK2 rearrangements, some of which appear to show CHL-like morphologic features. The presence of JAK2 rearrangements in cases of CD30+ PTCL augments current classification and may provide a therapeutic target via JAK2 inhibition. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.