title: Discordant intracellular and plasma D-2-hydroxyglutarate levels in a patient with IDH2 mutated angioimmunoblastic T-cell lymphoma.
abstract: OBJECTIVE
  Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with mutations in genes encoding isocitrate dehydrogenase1 and 2 (IDH1 and IDH2). Mutant IDH generates the oncometabolite D-2-hydroxyglutarate (D-2HG). We report the first case of discordant intracellular and plasma D-2HG levels in a patient with IDH2 R172S mutated AITL.
  
  
  METHODS
  An 87-year-old woman was diagnosed with AITL in the groin lymph node by morphologic and immunophenotypic analyses, and molecular studies by DNA sequencing. D-2HG was measured in both tumoral tissue and in pre-treatment plasma by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  While D-2HG was markedly elevated in the tissue sample, its level in plasma was normal. We discuss this discordant D-2HG result within the context of previously reported discordant 2HG results in other IDH mutated tumors, and its implication for using circulating D-2HG as a biomarker of IDH mutation. In addition, this case also harbored mutations in RHOA, TET2, and TP53. The molecular pathogenesis is briefly discussed.
  
  
  CONCLUSIONS
  While our case suggests that circulating D-2HG is not a reliable marker of IDH mutation in AITL, more cases need to be studied to arrive at a definite conclusion.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center Dallas, Texas.
authors.forename: Hywyn
authors.initials: H
authors.lastname: Churchill
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Texas Southwestern Medical Center Dallas, Texas.
authors.forename: Harris
authors.initials: H
authors.lastname: Naina
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Medical Center at Dallas Dallas, Texas.
authors.forename: Richard
authors.initials: R
authors.lastname: Boriack
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center Dallas, Texas ; Department of Pediatrics, University of Texas Southwestern Medical Center Dallas, Texas ; Department of Pathology and Laboratory Medicine, Children's Medical Center at Dallas Dallas, Texas.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center Dallas, Texas.
authors.forename: Weina
authors.initials: W
authors.lastname: Chen
mesh_terms: D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000473:pathology; D002853:Chromatography, Liquid; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D005260:Female; D005977:Glutarates / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D053719:Tandem Mass Spectrometry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005977:Glutarates; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C066737:RHOA protein, human; C019417:alpha-hydroxyglutarate; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; C541081:TET2 protein, human; D020742:rhoA GTP-Binding Protein
keywords: Angioimmunoblastic T-cell lymphoma; D-2-hydroxyglutarate; IDH mutation; RHOA mutation; TET2 mutation