Mycosis Fungoides/Sezary Syndrome Staging: Potential Pitfalls in Analyzing Bone Marrow and Lymph Nodes Using Flow Cytometric and Molecular Diagnostic Methods
KT Bradley, SS Parker, DL Jaye. Emory University Hospital, Atlanta, GA
Background: Staging of Mycosis Fungoides/Sezary Syndrome (MF/SS) often includes lymph node (LN) biopsy and for some patients bone marrow (BM) evaluation, and is crucial for determining prognosis and treatment. Histologic recognition of atypical lymphocytes is the gold standard for involvement by MF/SS. Flow cytometry (FC) and PCR for T-cell receptor gene rearrangements (TCR) aid in the diagnosis of blood involvement, but whether these tests provide accurate staging data for BM and LNs is unclear, particularly in patients with circulating neoplastic cells. Recently, the ISCL/EORTC proposed new subgroups for LN staging based on the results of TCR, and recommended tracking TCR data for BM specimens (Olsen et al, Blood 2007). In response, we sought to determine the incidence of discordant test results between morphology and FC/TCR in BM and LN specimens from MF/SS patients.
Design: We identified patients treated at our institution from 2000-2006 who had MF/SS and blood involvement. Data were reviewed for those who underwent a LN or BM biopsy for morphologic evaluation and FC and/or TCR. FC and TCR results were compared among blood, BM, LN, and skin biopsy specimens to confirm similarities in phenotype and base pair sizes of clonal peaks.
Results: 24 specimens (10 LN, 14 BM) from 12 patients were identified. For each patient, the phenotype and clonal peak sizes were the same among specimen types. 10 of 14 BM (71%) and 1 of 10 LN (10%) specimens showed discordance between the morphologic diagnosis and the FC or TCR results. In all discordant cases, morphology was negative while FC and/or TCR was positive (Figure).
Conclusions: Our data raise the possibility that FC and TCR are detecting blood-derived clonal cells contaminating BM and, to a lesser extent, LN samples rather than identifying true parenchymal disease. Thus, for MF/SS patients with blood disease, these findings will likely limit the ability to interpret FC- and TCR-based staging data for LNs and viscera in the absence of a test to resolve this issue. Given the rarity of MF/SS, multi-institutional studies investigating the prognosis of patients with blood disease and FC/TCR-positive, morphology-negative tissues are needed.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 174, Monday Morning