Expanded CD4+CD57+ T-large granular lymphocytes: A diagnostic pitfall in blood staging of mycosis fungoides/Sézary syndrome.

Objective: Accurate blood staging in mycosis fungoides (MF)/Sézary syndrome (SS) is essential for precise diagnosis, prognostication, and effective management. Through 3 illustrative cases, we highlight the complexity of blood staging of MF/SS caused by expanded CD4-positive T-cell large granular lymphocyte (T-LGL) populations that mimic malignant involvement and complicate accurate disease assessment.

Methods: We identified 3 patients with MF/SS and more than 250/µL of CD4-positive, CD7-negative and/or CD4-positive, CD26-negative T cells in blood but with discordant T-cell receptor profiles between blood and skin samples. We also analyzed 100 consecutive T-cell blood flow cytometry panels ordered for patients evaluated in our cutaneous lymphoma clinic to determine the frequency of such populations.

Results: Each case demonstrated expanded CD4-positive T-LGL populations in the blood characterized by at least partial CD8, CD56, and CD57 expression and absent or decreased CD26 and/or CD7 expression. Blood from these patients exhibited distinct clonotypes from skin lesions, suggesting a reactive rather than malignant origin. Analysis of 100 consecutive cutaneous lymphoma staging blood flow cytometry cases identified similar CD4-positive, CD57-positive T cells of 250/μL or more in 3 of 100 cases, plus 1 atypical case of SS with partial, dim CD57 expression.

Conclusions: The presence of expanded T-LGL populations in blood can confound accurate staging of MF/SS, potentially leading to misclassification and ineffective or unnecessary treatment. These cases exemplify how comprehensive molecular and immunophenotypic profiling, including multicolor flow cytometry and T-cell receptor comparisons, along with morphologic evaluation of blood ensure accurate disease assessment to inform better clinical decision-making in MF/SS.