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Previous Volume 331:154-160 July 21, 1994 Number 3 Next

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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[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 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.

Source Information

From the Departments of Pathology and Pediatrics, the Center for Molecular and Cellular Diagnostics, and the Cancer Center, University of New Mexico School of Medicine, Albuquerque (C.L.W., B.B.G., M.H.D.); the Division of Hematology-Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston (L.B., D.G.G.); the Department of Pathology and Laboratory Medicine, All Children's Hospital, St. Petersburg, Fla. (B.E.F.); and the Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston (K.L.M.)

Address reprint requests to Dr. Willman at the University of New Mexico Cancer Center, 900 Camino de Salud, N.E., Albuquerque, NM 87131.

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