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

Abstract

ABSTRACT 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/μL, neutropenia, and splenomegaly. In rare cases of so-called ‘aleukemic’ T-LGL leukemia, the number of LGLs is <400–500 cells/μL. 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.