{"title":"Detection of clonal histiocytes in Langerhans cell histiocytosis: biology and clinical significance.","authors":"C L Willman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although the first clinical description of Langerhans cell histiocytosis (LCH) was published over a century ago, the aetiology and pathogenesis of this enigmatic disorder are still remained unknown. Viral, immunological, neoplastic and other pathogenetic mechanisms have been considered, but none has been proven. The prevailing opinion is that LCH is a reactive disorder rather than a neoplastic process, but this presumption has never been definitively tested. A key feature of a neoplasm is its clonal derivation from a single cell. To determine if LCH is a polyclonal reactive or a clonal disorder, we and others have recently used molecular biological techniques to assess clonality in LCH. Using X chromosome-linked DNA probes that can detect clonal or polyclonal X chromosome inactivation patterns in female tissues, clonal CD1a+ histiocytes have now been detected in the lesional tissues in each of 16 females affected with LCH. Most of these patients were studied prior to the initiation of therapy. Lymphoid clonality was excluded in all cases in which it was studied, confirming that the clonal cells in LCH are the CD1a+ dendritic cells presumed to be pivotal in this disorder. Two distinct lesions (a pre-treatment bone biopsy and a lymph node biopsied 3 years later) have been studied in only one case to date; the same clonal pattern of X chromosome inactivation was observed, consistent with persistence of the same clone during this patient's disease course.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S29-33"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149702/pdf/brjcancersuppl00081-0035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18529085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multilevel therapeutic targeting by topoisomerase inhibitors.","authors":"P J Smith, S Souès","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The successful use of cytotoxic agents in the clinical management of LCH depends upon the selective targeting of cells participating in the disease process. The topoisomerase 'poisons', currently used extensively in the treatment of aggressive malignancies, represent an intriguing class of cytotoxic agents exerting their cytostatic and cytotoxic effects at multiple levels according to cell type. The non-DNA intercalating topoisomerase II poison, etoposide (VP-16), is the \"drug of first choice\" in the treatment of LCH by cytotoxic chemotherapy. This major anticancer agent traps the nuclear enzyme DNA topoisomerase II on DNA in a sequence-specific manner, the processing of trapped complexes giving rise to a plethora of cellular effects not least the potential activation of pathways leading to cell cycle arrest and apoptosis. This short review describes the principles of topoisomerase inhibition, the multiplicity of cellular effects and the concept of cellular targeting in LCH. The successful treatment of LCH by cytotoxic chemotherapy will depend on both the identity of the target tissues and a clear view of therapeutic intent, given the potential for induction of haematological neoplasia.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S47-51"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149715/pdf/brjcancersuppl00081-0053.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The origin of the Nikolas symposia.","authors":"I C Davis, A N Kontoyannis, J Pritchard","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S65-7"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149711/pdf/brjcancersuppl00081-0071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Viruses and Langerhans cell histiocytosis: is there a link?","authors":"K McClain, R A Weiss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>As a rare, sporadic disease Langerhans cell histiocytosis (LCH) presents a difficult problem in defining a likely etiology. Epidemiological data would not a priori lead one to choose a viral etiology. However, there are rare tumours which occur as sequelae of common infections from Epstein-Barr virus or human papilloma viruses. Likewise some viruses can cause cells to elaborate cytokines which could ultimately stimulate Langerhans cell growth. There is only a small amount of experimental data testing the hypothesis that viruses might be associated with LCH. The theoretical constructs surrounding this question and new data refuting the association are summarised.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S34-6"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149698/pdf/brjcancersuppl00081-0040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of cytokines in the pathogenesis of Langerhans cell histiocytosis.","authors":"G Kannourakis, A Abbas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Langerhans cell histiocytosis (LCH) is characterised by an accumulation of cells ('LCH cells') with the same phenotypic features as normal Langerhans cells found in skin and other organs. The pathogenesis of LCH is unknown but there is increasing evidence to implicate the involvement of lymphokines and proinflammatory cytokines in the tissue damage seen in this disorder. Apart from histiocytes, the lesions contain giant cells, macrophages, neutrophils, eosinophils, lymphocytes, plasma cells and occasional mast cells that are the hallmark of an inflammatory process. The role of cytokines in the recruitment of haemopoietic cells within inflammatory lesions has only recently been recognised. In this article, we review the possible role of cytokines in the pathogenesis of LCH, and provide an overview of the methods currently used to detect and quantitate them. An appreciation of the type, distribution and amount of different cytokines released within lesions can provide clues to the possible aetiology of LCH. Using immunoassays, in situ hybridisation and RT-PCR, increased amounts of IL-1, IL-3, IL-4, IL-8, GM-CSF, TNF alpha, TGF beta and LIF have been demonstrated in LCH lesions. Lymphocytes constitutively produce GM-CSF and IL-3 and, to a lesser degree, IL-1, IL-4 and LIF whilst histiocytes produce TNF alpha, IL-1 beta and GM-CSF.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S37-40"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149713/pdf/brjcancersuppl00081-0043.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The proceedings of the Nikolas Symposia on the Histiocytoses, 1989-1993.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S1-72"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18911937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Central nervous system disease in Langerhans cell histiocytosis.","authors":"N Grois, Y Tsunematsu, A J Barkovich, B E Favara","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes insipidus and anterior pituitary dysfunction, are familiar central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) but the pathophysiology and biological behaviour of other forms of CNS involvement in LCH are poorly understood. In an attempt to improve our understanding of these rare complications, we studied 23 patients with LCH in whom neuroradiological abnormalities, with or without neurological dysfunction other than diabetes insipidus, developed during the course of disease. Neuroradiological abnormalities were of three basic types (a) poorly-defined changes in white matter, (b) well-defined changes in white and grey matter and (c) extra-parenchymal \"tumoural\" masses. There was a profusion of associated neurological signs and symptoms in most cases but some patients were asymptomatic. The neuropathological features were complex but infiltration of the CNS by histiocytes with xanthomatous change, particularly prominent in mass lesions, was common in the 13 cases in which biopsies were done. Patients with lytic lesions of the skull and diabetes insipidus are evidently most at risk of developing these rare manifestations of LCH. Therapeutic questions could not be answered from this study because no standard treatment had been given and outcome varied widely.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S24-8"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149701/pdf/brjcancersuppl00081-0030.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current status of gene transfer into haemopoietic progenitor cells: application to Langerhans cell histiocytosis.","authors":"M Brenner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A number of recent studies have shown that it is possible to obtain significant levels of gene transfer and expression in marrow progenitor cells and their progeny by using retroviral vectors. The data obtained from these studies and the possible applications to Langerhans cell histiocytosis (LCH) are reviewed.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S56-7"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149717/pdf/brjcancersuppl00081-0062.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Langerhans cell histiocytosis--clinical and epidemiological aspects.","authors":"V Broadbent, R M Egeler, M E Nesbit","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Langerhans cell histiocytosis is a disease which frustrates both clinician and scientist. Its aetiology is unknown, its pathogenesis is ill understood and the clinical course is unpredictable. Historically, the different nomenclatures reflecting the first clinical descriptions by Hand (1893, 1921), Schuller (1915) and Christian (1920), and subsequently by Letterer (1924) and Siwe (1933), led to confusion only partially resolved by Lichtenstein (1953) who recognised that the disease in each of these clinical syndromes were components of a spectrum of disease involving the histiocyte. He proposed his unifying concept of Histiocytosis X--'X' being the unknown aetiological factor. In 1973, Nezelof recognised the lesional cell as a 'Langerhans-like' cell but it took another decade for the disease to be recognised as a single entity and the term Langerhans cell histiocytosis to be internationally accepted. The publication, by the Histiocyte Society (1987), of their classification of the histiocyte disorders together with criteria for pathological diagnosis and clinical evaluation of Langerhans cell histiocytosis have consolidated the position. This article details the wide variety of clinical manifestations of the disease and its sequelae and discusses possible epidemiological factors. Finally it looks at the potential implications of recent scientific research on the management of the disease.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S11-6"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149699/pdf/brjcancersuppl00081-0017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histiocytosis--an introduction.","authors":"J Pritchard, V Broadbent","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Histiocytoses are a group of rare and puzzling multisystem disorders, currently regarded as non-malignant but often treated with 'cancer chemotherapy'. In this article, the origins of histiocytes and of the Histiocyte Society's classification of the Histiocytoses are described with suggested minor modifications to the classification. The current nomenclature for the 2 principal diseases, now named 'Langerhans cell histiocytosis' and 'Haemophagocytic Lymphohistiocytosis', is less confusing than the terms originally chosen. The article sets the scene for the succeeding papers, which focus on 'Langerhans cell histiocytosis'.</p>","PeriodicalId":76609,"journal":{"name":"The British journal of cancer. Supplement","volume":"23 ","pages":"S1-3"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149703/pdf/brjcancersuppl00081-0007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19068512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}