# How We Evaluate and Treat Leukemic Presentations of Mature T-Cell Lymphomas

## TL;DR

This paper reviews how to diagnose and treat rare leukemias caused by mature T-cells, focusing on distinguishing them from non-cancerous conditions.

## Contribution

The paper provides a structured diagnostic and management approach for four subtypes of mature T-cell leukemias.

## Key findings

- Mature T-cell leukemias are rare and require a systematic approach to differentiate from benign T-cell clonality.
- The paper outlines clinical features, workup, and treatment options for four major subtypes of these leukemias.
- Diagnostic challenges include distinguishing clonal T-cell lymphocytosis from non-malignant conditions.

## Abstract

Mature T-cell lymphomas (TCLs) are classified based on their predominant site of involvement as peripheral TCLs, cutaneous TCLs, mature T-cell leukemias and extranodal TCLs. Mature T-cell leukemias are characterized by clonal T-cell lymphocytosis but the differential diagnosis of clonal T cells includes non-malignant conditions. Furthermore, the diagnostic evaluation of mature T-cell leukemias can be challenging and treatment is specific to subtypes, making it important to follow a structured approach to obtain an accurate diagnosis. In this review we outline a comprehensive approach to diagnosis and management of mature T-cell leukemias.

T-cell non-Hodgkin lymphomas, which arise from post-thymic mature T cells, constitute approximately 10–15% of all non-Hodgkin lymphomas. Their leukemic presentations, referred to here as mature T-cell leukemias, are relatively uncommon and present significant diagnostic and therapeutic challenges requiring an informed approach to diagnosis and management. The initial presentation is often persistent T-cell lymphocytosis that must be distinguished from reactive (non-malignant) causes. Unlike B-cell lymphocytosis, where clonality usually indicates malignancy, T-cell clonality can be detected in benign conditions such as autoimmune disorders and viral infections. Thus, establishing clonality is helpful but not sufficient, and a systematic diagnostic approach integrating clinical features, morphology, immunophenotype, and molecular findings is critical. This review outlines our approach to the diagnosis and treatment of four major subtypes of mature T-cell leukemias: T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), T-large granular lymphocytic leukemia (T-LGL), and Sézary syndrome (SS). Each section includes a discussion of clinical features, workup, and treatment options.