The diagnosis of mature T-cell lymphoid neoplasms can be particularly challenging due to their overlapping features with reactive T cells. However, the development of specific antibodies targeting the mutually exclusive β-chain isoforms of the T-cell receptor, TRBC1 and TRBC2, has made it possible to assess the restriction of these chains and establish clonality evaluation. This report presents an uncommon case with an immunophenotype suggestive of “T-cell Large Granular Lymphocytic Leukemia,” characterized by the presence of two clones: one in the CD4 compartment exhibiting TRBC1 monoclonality and another in the CD8 compartment exhibiting TRBC2 monoclonality.

A 66-year-old male patient with a normal physical examination. The complete blood count showed: hemoglobin 5.27 g/dL, platelets 207,000/mm³, leukocytes 16,000/mm³, neutrophils 6,864/mm³, eosinophils 448/mm³, monocytes 928/mm³, and 7,696/mm³ lymphoid cells with a mature appearance, nuclear irregularities, and abundant granular cytoplasm. A peripheral blood sample was submitted for immunophenotypic evaluation by flow cytometry, which revealed 33.8% T lymphocytes expressing CD2, CD3, CD5 (dim expression), CD56, CD57, and TCR alpha/beta. Of these cells, 20.9% exclusively expressed CD4 and TRBC1, while 12.9% exclusively expressed CD8 and TRBC2, identifying two distinct populations of monoclonal T lymphoid cells with an immunophenotype consistent with T-cell "Large Granular" lymphoid cells.

The diagnosis of mature T-cell lymphoid malignancies is complex and often challenging due to the immunophenotypic overlap between neoplastic T cells and non-neoplastic reactive T cells. The development and implementation of specific antibodies have led to significant advances in clonality assessment. Among these markers, TRBC1 and TRBC2 are especially useful in identifying specific neoplastic clones. The use of these markers has greatly improved the differentiation between neoplastic and reactive T cells, thereby increasing diagnostic accuracy.

We report a rare case of two distinct mature T-cell lymphoid clones in a case suggestive of “T-cell Large Granular Lymphocytic Leukemia,” with few prior cases documented in the literature. This highlights the importance of assessing T-cell clonality using TRBC1 and TRBC2 markers. Advances in this field have been crucial for achieving faster and more accurate diagnoses, which in turn facilitate more effective treatments and better clinical outcomes.