title: Diagnostic challenges in the work up of hypereosinophilia: pitfalls in bone marrow core biopsy interpretation.
abstract: The FIP1L1-PDGFRA (FP) fusion gene is identified in a substantial proportion of patients with eosinophilia-associated myeloproliferative neoplasms (MPN-eo) who subsequently achieve rapid and durable remissions on imatinib. In the initial diagnostic work-up of hypereosinophilia (HE), histologic and immunohistochemical evaluation of a bone marrow (BM) core biopsy is considered essential for the differentiation between reactive hypereosinophilia (HER), MPN-eo and hypereosinophilic syndrome (HES). We therefore retrospectively analysed the initial reports of BM core biopsies from 116 patients who were subsequently identified as FP positive (FP+, n = 56) or FP negative/corticosteroid-responsive HER or HES (n = 60). Compared to HER or HES, detection of FP was more frequently associated with increased numbers of blasts (11/56 vs. 2/60, p = 0.007) and mast cells (23/33 vs. 7/23, p = 0.006; with expression of CD25 [11/18 vs. 2/13, p = 0.025]), and/or fibrosis (25/35 vs. 1/23, p < 0.0001). In FP+ patients, HE was correctly associated with an underlying clonal haematologic disorder in only 36/56 (64 %) of cases, but final BM diagnoses included a variety of diagnoses such as MPN-eo (n = 15), acute myeloid leukaemia (n = 8), systemic mastocytosis (n = 6), chronic myeloid leukaemia (n = 5) or unclassified MPN (n = 2). We conclude that the final evaluation of BM core biopsies in the diagnostic work-up of HE should include comprehensive morphologic (stains for myeloid blast cells, mast cells and fibres) and genetic analyses before a final diagnosis is established.
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Schwaab
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Jawhar
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Naumann
authors.affiliation: Institut für Pathologie, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Fabarius
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horny
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.|Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany. andreas.reiter@medma.uni-heidelberg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.affiliation: III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000379:methods / Q000592:standards; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
chemical_list: D015514:Oncogene Proteins, Fusion; D039221:mRNA Cleavage and Polyadenylation Factors; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: Bone marrow histology; FIP1L1-PDGFRA; Hypereosinophilia; Misdiagnosis