[1351] Detection of Clonal Lymphoid Receptor Gene Rearrangements in Langerhans Cell Histiocytosis

Q Huang, W Chen, J Wang, E Wang, Y Lu, SK Lau, LM Weiss. City of Hope National Medical Center, Duarte, CA; Loma Linda University Medical Center, Loma Linda, CA; Duke University Medical Center, Durham, NC

Background: Langerhans cell histiocytosis (LCH), also known as histiocytosis X, is a rare disorder characterized by an abnormal accumulation and/or clonal proliferation of Langerhans cells (LCs) in various body organs. The cellular origin of LCs has been a subject of considerable debate since their discovery. LCs are generally considered to be of myeloid origin from the bone marrow, however, recent studies in mice have demonstrated that LCs can be derived from lymphoid-committed CD4low precursors, suggesting a lymphoid origin. In human LCH, concomitant or sequential occurrence of a lymphoid or myeloid malignancy has been occasionally reported, suggesting the presence of lineage plasticity and/or the possibility of transdifferentiation of two otherwise morphologically and immunophenotypically different neoplasms.
Design: We retrospectively investigated 46 well-characterized LCH cases to detect clonal rearrangements of T cell receptor gamma gene (TCRγ) and immunoglobulin heavy chain and kappa light chain genes (IgH/IgK). In addition, q-PCR analysis for t(14;18) translocation of these lesions was also performed.
Results: The study included 25 males and 21 females, with ages ranging from <1 to 59 years. None (0/46) of the cases had a known history or concurrent B or T-cell lymphoma. Of 46 cases, 30% (14/46) cases had clonal IgH (4 cases), IgK (5 cases) or TCRγ (9 cases) gene rearrangements, respectively. Interestingly, of the 14 cases with at least one clonal rearrangement of lymphoid receptor genes, 3 LCH cases were demonstrated to have both TCRγ and IgH/IgK gene rearrangements, suggesting lineage plasticity or infidelity of the neoplasm. Furthermore, all of the 14 cases were negative for t(14;18) by quantitative PCR analysis.
Conclusions: Our study demonstrates that lymphoid receptor gene rearrangements can be detected in a subset of sporadic LCH cases, suggesting a possible lineage relationship between LCs and lymphoid cells. The results provide genotypic evidence supporting the notion of lineage plasticity of hematopoietic cells as well as their associated neoplasms.
Category: Hematopathology

Monday, March 22, 2010 1:15 PM

Platform Session: Section B, Monday Afternoon


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