Original ArticlesAngioimmunoblastic T-Cell Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma A Novel Form of Composite Lymphoma Potentially Mimicking Richter SyndromeTrimech, Mounir MD, PhD*; Letourneau, Audrey PhD*; Missiaglia, Edoardo PhD*; De Prijck, Bernard MD†; Nagy-Hulliger, Monika MD‡; Somja, Joan MD, PhD§; Vivario, Manuela MD§; Gaulard, Philippe MD∥,¶,#; Lambert, Frédéric MD, PhD**; Bisig, Bettina MD, PhD*; de Leval, Laurence MD, PhD* Author Information *Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and Lausanne University, Lausanne ‡Service of Hematology, Hospital of Morges, Morges, Switzerland †Department of Medicine, Division of Hematology §Department of Pathology, University Hospital of Liège **Molecular Hemato-Oncology Unit, Center for Human Genetic, UniLab Liège, University Hospital of Liège, Liège, Belgium ∥Department of Pathology, Henri Mondor Hospital, AP-HP ¶INSERM U955, Mondor Institute for Biomedical Research (IMRB) #Paris Est Creteil University, Créteil, France B.B. and L.d.L. contributed equally. Conflicts of Interest and Source of Funding: Supported by a grant of the National Swiss Foundation. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Laurence de Leval, MD, PhD, Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, 25 rue du Bugnon, Lausanne CH-1011, Switzerland (e-mail: [email protected]). The American Journal of Surgical Pathology 45(6):p 773-786, June 2021. | DOI: 10.1097/PAS.0000000000001646 Buy SDC Metrics Abstract Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neoplasm that may transform into a clinically aggressive disease, namely Richter syndrome, usually as diffuse large B-cell lymphoma. Besides, CLL/SLL encompasses an increased risk of developing other secondary cancers, including a variety of T-cell lymphomas, often of the anaplastic large-cell type or with a cytotoxic phenotype. Here, we report a small series of patients with composite lymphomas consisting of CLL/SLL and angioimmunoblastic T-cell lymphoma (AITL), a hitherto unrecognized association. The 3 patients (1 male/2 females, 68 to 83 y) presented with high-grade-type symptoms. One patient was clinically suspicious for Richter syndrome, in the others CLL/SLL and AITL were concomitant de novo diagnoses. CLL/SLL and AITL were admixed in the same lymph nodes (3/3 cases) and in the bone marrow (1/2 cases). In all cases, the AITL comprised prominent clear cells with a strong T follicular helper immunophenotype and similar mutations consisting of TET2 or DNMT3A alterations, IDH2 R172K/M, and RHOA G17V. The 3 patients received chemotherapy. One died of early AITL relapse. The other 2 remained in complete remission of AITL, 1 died with recurrent CLL, and 1 of acute myeloid leukemia. These observations expand the spectrum of T-cell lymphoma entities that occur in association with CLL/SLL, adding AITL to the rare variants of aggressive neoplasms manifesting as Richter syndrome. Given that disturbances of T-cell homeostasis in CLL/SLL affect not only cytotoxic but also helper T-cell subsets, these may contribute to the emergence of neoplasms of T follicular helper derivation. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.