Aleukemic variant of T-cell large granular lymphocyte leukemia in patients with rheumatoid arthritis - diagnostically challenging subtype

Introduction: The typical clinical manifestations of T-cell large granular lymphocyte (T-LGL) leukemia are an increase in the number of large granular lymphocytes (LGLs) in the blood > 2000 cells/mu L, neutropenia, and splenomegaly. In rare cases of so-called 'aleukemic' T-LGL leukemia, the number of LGLs is <400-500 cells/mu L. In patients with rheumatoid arthritis (RA), distinguishing T-LGL leukemia with low tumor burden in the blood and bone marrow from Felty syndrome (FS) poses diagnostic challenges. Areas covered: This review aimed to describe the basic characteristics and variants of aleukemic T-LGL leukemia, with a special focus on aleukemic T-LGL leukemia with massive splenomegaly (splenic variant of T-LGL leukemia) and differential diagnosis of such cases with hepatosplenic T-cell lymphoma. The significance of mutations in the signal transducer and activator of transcription 3 (STAT3) gene for distinguishing aleukemic RA-associated T-LGL leukemia from FS is discussed, along with the evolution of the T-LGL leukemia diagnostic criteria. PubMed database was used to search for the most relevant literature. Expert opinion: Evaluation of STAT3 mutations in the blood and bone marrow using next-generation sequencing, as well as a comprehensive spleen study, may be necessary to establish a diagnosis of aleukemic RA-associated T-LGL leukemia.