Flow Cytometry for Diagnosing Sézary Syndrome When Skin Biopsies Are Inconclusive: A Case Report

Abstract

Sézary syndrome (SS) is a rare leukemic variant of cutaneous T-cell lymphomas, accounting for a small proportion of cases, estimated at less than 5% of all cutaneous T-cell lymphomas, characterized by pruritic erythroderma, lymphadenopathy, and circulating clonal T lymphocytes. Diagnosis can be challenging when skin biopsies are non-diagnostic, potentially delaying treatment. Peripheral blood flow cytometry (FC) is essential for detecting aberrant T-cells, assessing clonality, which may be supported in selected cases by T-cell receptor beta-chain constant region 1 (TRBC1) expression analysis, quantifying tumor burden, and guiding tumor-node-metastasis-blood (TNMB) staging and follow-up. A 58-year-old man presented with diffuse pruritic erythroderma and lesions refractory to topical corticosteroids, systemic corticosteroids, methotrexate, and emollients. Repeated skin biopsies showed spongiotic or psoriasiform changes without evidence of malignancy. Peripheral blood smear revealed 5-7% Sézary cells. FC identified an aberrant cluster of differentiation (CD)4+ T-cell population representing 90% of lymphocytes, with CD7+, CD26-, and 97% TRBC1 positivity, confirming a clonal malignant population. Lymph node biopsy was consistent with T-cell lymphoma. TNMB classification was T4N3M0B2 (stage IVA2). The patient received peginterferon alfa-2a with topical corticosteroids and supportive care, leading to clinical and laboratory improvement. This case underscores the critical role of FC when skin biopsies are inconclusive. Comprehensive immunophenotyping, including TRBC1, confirms monoclonality, informs TNMB staging, and guides targeted therapy. Quantitative assessment of circulating malignant cells allows dynamic monitoring of treatment response. Early integration of peripheral blood FC in suspected SS improves diagnostic accuracy, reduces delays, and enables rapid initiation of targeted therapy, ultimately optimizing patient outcomes.