title: Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis.
abstract: Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, fatal disorder of infancy. We report here a 17-day-old female infant who presented with high fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, thrombocytopenia, and liver failure. Leukocytosis was detected with circulating "atypical" lymphoid cells. Flow cytometric studies revealed expanded subpopulations of CD8+ T cells with unusual immunophenotypic features, including a subset that lacked CD5 expression. A liver biopsy showed hemophagocytic lymphohistiocytosis with exuberant infiltrates of CD8+ T cells that lacked perforin. Mutational studies revealed a 666C-->A (H222Q) missense mutation in the perforin gene. T-cell receptor studies on flow-sorted T-cell subpopulations revealed no evidence of monoclonality. Analysis of T-cell receptor excision circle levels indicated long proliferative history in the aberrant CD8+ T-cell subsets. This case provides an instructive example of uncontrolled reactive proliferation of CD8+ T cells in FHL, resulting in atypical morphology and unusual immunophenotypic features that might suggest malignancy in other clinical settings.
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 75390-9072, USA. nitin@pathology.swmed.edu
authors.forename: Nitin J
authors.initials: NJ
authors.lastname: Karandikar
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kroft
authors.forename: Subramanian
authors.initials: S
authors.lastname: Yegappan
authors.forename: Beverly B
authors.initials: BB
authors.lastname: Rogers
authors.forename: Victor M
authors.initials: VM
authors.lastname: Aquino
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Guenaga
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Robert W
authors.initials: RW
authors.lastname: McKenna
mesh_terms: D001706:Biopsy; D018956:CD5 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D004252:DNA Mutational Analysis; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D019675:Genes, T-Cell Receptor gamma / Q000235:genetics; D015616:Histiocytosis, Non-Langerhans-Cell / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D020125:Mutation, Missense; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D018956:CD5 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin