Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578833
Title: Investigating lesions of Langerhans cells and their role in lymphoproliferative diseases
Author: Christie, Lesley Jane
Awarding Body: University of Dundee
Current Institution: University of Dundee
Date of Award: 2011
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Abstract:
Langerhan’s cells (LCs) are the immune sentinels of the skin, sampling the cutaneous microenvironment and presenting captured antigen to T cells. A sheet-like proliferation of LCs is termed Langerhan’s cell histiocytosis (LCH), an enigmatic and poorly understood disorder with a widely varied clinical spectrum and disease course. In non-pulmonary LCH all cases reported to date have been monoclonal. Clonality argues for LCH as a neoplastic rather than reactive disorder. After initial investigation of the limitations of formalin fixed paraffin embedded tissues for downstream analysis, lesions of LCH were collected from 4 sites across Scotland. To further define the spectrum of LCH, clonality was assessed using an X inactivation assay based on the polymorphous region of the Human Androgen Receptor. To improve understanding of the assay, a study on post-mortem material was undertaken. This demonstrated a unique insight into patterns of X inactivation across different tissues of the same individual and highlighted potential pitfalls in interpretation. An important question was whether lesions of LCH associated with haematopoietic neoplasms were polyclonal or monoclonal proliferations? For the first time, associations of LCH with B-cutaneous lymphoid hyperplasia (B-CLH), lymphomatoid papulosis (LyP) and mycosis fungoides (MF) are reported. In two female cases, the LCs were polyclonal providing some reassurance that such lesions are reactive in nature and should not be regarded as potential second neoplasms. In a more expanded study a wide variety of primary LCH lesions were assessed for clonality. Significant limitations were posed by the quality of the material available; in 2 cases the lesions were found to be polyclonal. This is the first time such a result has been reported. Monoclonality was identified in 2 other cases including one of pulmonary LCH. The findings reported herein suggest that clonality and hence neoplasia cannot be assumed in all cases of primary non-pulmonary LCH. The possible functions of LCs in cutaneous lymphoma were explored. In T-cell lymphoma 2 cases reported here suggest a role for LCs in disease progression. In contrast, LCs play no significant part in the development or progression of cutaneous B-cell proliferations although other types of dendritic cells probably have an important role. By studying proliferations of LCs in a variety of settings, this work has extended knowledge of the spectrum of LCH. Displaying similar histopathological appearances, lesions of LCH may be best defined by clonality as well as cytokine expression and level of maturation. In future, such markers may be employed as prognostic indicators allowing individualised and targeted management.
Supervisor: Not available Sponsor: Royal College of Pathologists, Jean Shanks Fellowship
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.578833  DOI: Not available
Keywords: Langerhans ; Clonality ; Dendritic ; X inactivation ; Skin
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