title: Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease.
abstract: BACKGROUND
  The lesions of Langerhans'-cell histiocytosis (histiocytosis X), a proliferative histiocytic disorder of unknown cause, contain histiocytes similar in phenotype to dendritic Langerhans' cells. The disease ranges in severity from a fatal leukemia-like disorder to an isolated lytic lesion of bone. Intermediate forms of the disease are usually characterized by multiorgan involvement, diabetes insipidus, and a chronic course.
  
  
  METHODS
  To determine whether Langerhans' histiocytosis is a polyclonal reactive disease or a clonal disorder, we used X-linked polymorphic DNA probes (HUMARA, PGK, M27 beta[DXS255], and HPRT) to assess clonality in lesional tissues and control leukocytes from 10 female patients with various forms of the disease. Lymphoid clonality was also assessed by analysis of rearrangements at immunoglobulin and T-cell-receptor gene loci.
  
  
  RESULTS
  The HUMARA assay detected clonal cells in the lesions of 9 of the 10 patients: 3 patients had acute disseminated disease, 3 had unifocal disease, and 3 had intermediate forms. The percentage of clonal cells closely approximated the percentage of CD1a-positive histiocytes in each lesion. Clonality was also confirmed in two of nine cases with the PGK or M27 beta probe. Extreme constitutional lyonization precluded assessment of clonality in the 10th case. Lymphoid clonality was ruled out in all cases.
  
  
  CONCLUSIONS
  The detection of clonal histiocytes in all forms of Langerhans'-cell histiocytosis indicates that this disease is probably a clonal neoplastic disorder with highly variable biologic behavior. Thus, genetic mutations that promote clonal expansion of Langerhans' cells or their precursors may now be identified.
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque.
authors.forename: C L
authors.initials: CL
authors.lastname: Willman
authors.forename: L
authors.initials: L
authors.lastname: Busque
authors.forename: B B
authors.initials: BB
authors.lastname: Griffith
authors.forename: B E
authors.initials: BE
authors.lastname: Favara
authors.forename: K L
authors.initials: KL
authors.lastname: McClain
authors.forename: M H
authors.initials: MH
authors.lastname: Duncan
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D017931:DNA Primers; D015342:DNA Probes; D005260:Female; D006644:Histiocytes; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D015342:DNA Probes