Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis

Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 75390-9072, USA.
Blood (Impact Factor: 10.45). 11/2004; 104(7):2007-9. DOI: 10.1182/blood-2004-04-1431
Source: PubMed


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.

Download full-text


Available from: Elaine S Jaffe
  • [Show abstract] [Hide abstract]
    ABSTRACT: Histiocytic disorders are diseases characterized by the proliferation and/or accumulation of histocytic cells in bone marrow (BM), peripheral blood (PB), and a variety of extramedullary tissues, associated with variable local and systemic symptoms, which depend on the disease subtype. Histiocytes are hematopoietic cells that derive from BM progenitors and have important functions in the immune system, including antigen presentation and antigen processing. Normal histiocytes include multiple functional subsets with distinct morphology, immunophenotype, and tissue localization. Histiocytic dis-orders are currently classified according to their morphologic and immunophenotypic resemblance to these normal counterparts, as well as according to their clinical presentation and biologic behavior (Table 42.1). The immunohistochemical classification of the tumors of histiocytes and accessory dendritic cells proposed by the International Lymphoma Study Group comprises two major categories: disorders of varied biologic behavior and malignant disorders. This chapter will focus on the former category, which includes clonal and non-clonal entities, none of which may be definitively classified as malignant, although their clinical behavior may be aggressive and even fatal (Table 42.2). The malignant disorders include sarcomas with histiocytic or dendritic cell differentiation, as well as acute myeloid leukemias (AMLs) with monocytic or monoblastic differentiation. Due to the rarity and thus lack of a significant amount of molecular data, sarcomas with histiocytic or dendritic cell differentiation will not be addressed in this chapter. For a discussion of AMLs with monocytic or monoblastic differentiation, see Chaps. 34 and 35.
    No preview · Article · Jan 2010
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Histiocytic disorders occur with increased frequency in children and young adults. The wide spectrum of neoplastic and nonneoplastic diseases characterized by histiocytic proliferation was reflected in the cases submitted to the 2003 Society for Hematopathology and the European Association for Haematopathology Workshop. This review focuses on the entities represented at the workshop. It includes an overview of the classification and immunophenotype of the histiocytic disorders. The clinical and pathologic features of each entity are illustrated with representative cases submitted to the workshop, with an emphasis on recent biologic and genetic insights. In addition, a brief review of the pathologic features of the lysosomal storage disorders is included, with an emphasis on findings relevant to the practicing hematopathologist, exemplified with cases presented at the workshop.
    Preview · Article · Jan 2005 · American Journal of Clinical Pathology

  • No preview · Article · Aug 2006 · Leukemia and Lymphoma
Show more