Pedro Horna1, Lynn C Moscinski2, Lubomir Sokol3, Haipeng Shao2. 1. Division of Hematopathology, Mayo Clinic, Rochester, Minnesota. 2. Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center, Tampa, Florida. 3. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida.
Abstract
BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are clinically distinct cutaneous T-cell lymphomas with strikingly similar morphologic and phenotypic features. Prior studies have suggested phenotypic differences based on markers of antigen experience, suggesting a different cell of origin. METHODS: Seventy-nine involved peripheral blood or bone marrow samples from 33 patients with SS and 19 patients with MF were studied by 10-color flow cytometry, including CD62L, CD45RA, CCR4, and PD-1. Gated tumor events were classified as naïve (TN ), central memory (TCM ), effector memory (TEM ), or effector memory with reacquired CD45RA (TEMRA ); based on CD62L+ /CD45RA+ , CD62L+ /CD45RA- , CD62L- /CD45RA- , or CD62L- /CD45RA+ phenotype, respectively. Sequential specimens were compared to assess for phenotypic stability. RESULTS: The naïve/memory phenotype of the neoplastic T-cells was markedly heterogeneous, with a dominant TN , TCM , TEM , or TEMRA subset on 11 (14%), 32 (41%), 30 (38%), and 6 (8%) cases, respectively. There was no correlation between the diagnosis of MF or SS and putative cell of origin (P = 0.4). Overexpression of CCR4 and PD1 was observed in most cases, with higher intensity in SS compared to MF. The naïve/memory phenotype remained the same for 10 patients up to 273 days after the initial analysis; while on six patients, the naïve/memory phenotype was different from the original phenotype. CONCLUSIONS: Both SS and MF can have phenotypic features of any of the major naïve/memory T-cell subsets, which questions the current principle of "cell-of-origin" distinction between SS and MF. Phenotypic shifts within these subsets are common, suggesting a functional state rather than a cell-of-origin surrogate.
BACKGROUND:Mycosis fungoides (MF) and Sézary Syndrome (SS) are clinically distinct cutaneous T-cell lymphomas with strikingly similar morphologic and phenotypic features. Prior studies have suggested phenotypic differences based on markers of antigen experience, suggesting a different cell of origin. METHODS: Seventy-nine involved peripheral blood or bone marrow samples from 33 patients with SS and 19 patients with MF were studied by 10-color flow cytometry, including CD62L, CD45RA, CCR4, and PD-1. Gated tumor events were classified as naïve (TN ), central memory (TCM ), effector memory (TEM ), or effector memory with reacquired CD45RA (TEMRA ); based on CD62L+ /CD45RA+ , CD62L+ /CD45RA- , CD62L- /CD45RA- , or CD62L- /CD45RA+ phenotype, respectively. Sequential specimens were compared to assess for phenotypic stability. RESULTS: The naïve/memory phenotype of the neoplastic T-cells was markedly heterogeneous, with a dominant TN , TCM , TEM , or TEMRA subset on 11 (14%), 32 (41%), 30 (38%), and 6 (8%) cases, respectively. There was no correlation between the diagnosis of MF or SS and putative cell of origin (P = 0.4). Overexpression of CCR4 and PD1 was observed in most cases, with higher intensity in SS compared to MF. The naïve/memory phenotype remained the same for 10 patients up to 273 days after the initial analysis; while on six patients, the naïve/memory phenotype was different from the original phenotype. CONCLUSIONS: Both SS and MF can have phenotypic features of any of the major naïve/memory T-cell subsets, which questions the current principle of "cell-of-origin" distinction between SS and MF. Phenotypic shifts within these subsets are common, suggesting a functional state rather than a cell-of-origin surrogate.
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