Molecular Detection of Circulating Sezary Cells in Patients with Mycosis Fungoides
CB Hutchinson, E Wang. Duke University Medical Center, Durham, NC
Background: Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma and prognosis depends on clinical stage. While patients with disease confined to the skin have an excellent prognosis, advanced stage, Sezary Syndrome (SS) particularly, carries a worse outcome. We investigate circulating Sezary cells in MF patients by using PCR based T-cell receptor (TCR) gene rearrangement studies, in addition to flow cytometry and morphologic examination.
Design: 104 patients were identified with clinical findings/skin biopsy consistent with MF. All had flow cytometric immunophenotyping of peripheral blood. 96 cases had TCR gene rearrangement studies on peripheral blood; 78 had TCR analysis on skin biopsy. Retrospective analysis was performed and the rate of positivity for each test was determined. Clonal PCR products were compared in cases with positive PCR in both peripheral blood and skin to determine the rate of true positivity (positive predictive value).
Results: Of 104 cases, 16 (15.4%) showed circulating Sezary cells by flow cytometry. Of 83 cases with negative flow cytometry and TCR gene rearrangement performed on peripheral blood, 22 (26.5%) showed clonal rearrangements. 74 cases had TCR gene rearrangement studies on both peripheral blood and skin. Of these, 15 cases had clonal peaks in both peripheral blood and skin. Of those 15 cases, 7 were positive by flow cytometry and had matching base pair length of clonal peaks in the peripheral blood and skin. Of the remaining 8 cases with negative flow cytometry, 5 (62.5%) demonstrated matching clonal peaks in the peripheral blood and skin. 3 of those 8 cases (37.5%) showed different clonal peaks, likely representing false positives. Given a 62.5% positive predictive value for 26.5% of cases (22/83), the matching rate for clonal PCR products in the peripheral blood and skin is projected to be 16.56% among 83 cases with negative flow cytometry.
Conclusions: Of cases with no detectable circulating Sezary cells, 26.5% show clonal TCR gene rearrangement in peripheral blood. The positive predictive value for this is 62.5% based on matching base pair length of PCR products in blood and skin; thus, the projected rate of matching clonal products is 16.5%. This may represent subclincal circulating Sezary cells. 2 cases had follow up flow cytometry, 1 of which demonstrated circulating Sezary cells 7 months later and subsequently developed SS. More follow up is needed to determine the significance of a subclinical circulating clone and the utility of molecular monitoring for early identification of disease progression.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 68, Monday Morning