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

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.

KEYWORDS:

• Rheumatoid arthritis
• T-cell large granular lymphocyte leukemia
• STAT3
• Felty’s syndrome
• aleukemic leukemia

Article highlights

• An atypical (aleukemic) variant of T-LGL leukemia exists, where the number of LGLs in the peripheral blood is <400 − 500 cells/μL.

• The splenic variant of T-LGL leukemia is characterized by massive splenomegaly due to infiltration of the red pulp by clonal cytotoxic T-LGLs, neutropenia, and no or minimal tumor involvement in the bone marrow and peripheral blood.

• The detection of STAT3 mutations in patients with RA and neutropenia, despite the absence of a dominant T-cell clone in the blood and bone marrow, indicates T-LGL leukemia with a low tumor burden or NK-LGL leukemia.

• Felty syndrome can only be diagnosed after ruling out T- or NK-cell LGL leukemia.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contributions

All authors have made substantial contributions to the work and have approved the submitted version.

Additional information

Funding

This paper was not funded.