’Idiopathic’ Eosinophilia with an Occult T-Cell Clone: Prevalence, FIP1L1-PDGFRA Status, and Clinical Course.
Authors: Pardanani Animesh , Vaklavas Christos , Butterfield Joseph , Ketterling Rhett , Verstovsek Srdan , Kantarjian Hagop , Tefferi Ayalew 
Published: October 2019

Abstract
Background: Blood eosinophilia results either from autonomous expansion of a myeloid stem/progenitor cell, or as a response to cytokines that promote growth and differentiation of eosinophil progenitors. A subset of patients with hypereosinophilic syndrome/idiopathic eosinophilia (HES/IE) display abnormal T-cell immunophenotype and/or clonal rearrangements of the T-cell receptor (TCR), operationally assigned the term “lymphocyte variant” HES/IE. Information on the prevalence, FIP1L1-PDGFRA status, and clinical course of such patients is limited.
Methods: Consecutive patients with eosinophilia were identified by querying our institutional electronic database from 1995 to 2004. Clonal rearrangements of the γchain of the TCR were identified by polymerase chain reaction followed by gel electrophoresis in all cases, and confirmed by Southern Blot analysis of the gene coding for the β chain of the TCR, using standard methods. FIP1L1-PDGFRA was screened by fluorescence in situ hybridization.
Results: We studied a total of 205 consecutive patients with eosinophilia defined as an absolute eosinophil count (AEC) of > 600/μL, who also had a bone marrow study performed. Of these, TCR gene rearrangements studies were performed in 99 patients (AEC range of 650 to 38,000/μL) including 3 children and 96 adults (age range 18 to 88 years; 58 males). Among these 99 patients, 14 (~14%) had a demonstrable T-cell clone in peripheral blood, bone marrow aspirate, lymph node, and/or skin. Six of the 14 patients with a demonstrable T-cell clone were found to have a concurrent T-cell malignancy at the time of evaluation including T-cell large granular lymphocytic (T-LGL) leukemia - 1 case and peripheral T-cell lymphoma - 5 cases. The other 8 (~8%) patients otherwise fulfilled the working diagnosis of “lymphocyte variant” HES/IE (median AEC=2045/μL, range 720/μL to 9600/μL). The median duration of eosinophilic prodrome, prior to identification of the occult T-cell clone was 5 years (range 3 months to 11 years), and virtually all had dominant skin involvement presenting as dermatitis (5 cases) or episodic angioedema with eosinophilia (EAE) (2 cases). Five of 7 patients tested had an elevated serum IgE level, and a similar proportion displayed an abnormal T-cell immunophenotype (most commonly, aberrant CD5 and/or CD7 expression). Six of the 8 patients with an occult T-cell clone were evaluated for FIP1L1-PDGFRA and tested negative. Two patients were effectively treated with low-dose oral cyclophosphamide or methotrexate (follow-up duration of 3+ and 6+ years, respectively) whereas imatinib treatment was ineffective in another 2 patients. Two patients (25%) transformed into cutaneous T-cell lymphoma after 3 to 8 years of eosinophilic prodrome.
Conclusion: The current study suggests that the presence of a T-cell clone in idiopathic eosinophilia is a marker/harbinger of a primarily skin-based peripheral T-cell lymphoma that responds to T cell-directed therapy but not imatinib therapy, which is consistent with the absence of FIP1L1-PDGFRA in such cases.