Tumour ReviewLangerhans cell sarcoma: A systematic review
Introduction
Langerhans cells function as antigen presenting cells within the histiocyte system. These are found in the supra-basal region of mucous membranes and the dermis, lymph nodes and the thymus gland and play a role in the immune response. The histiocyte system is divided into two cellular subsets: phagocytic cells (antigen processing cells) and dendritic cells (antigen presenting cells). Dendritic cells comprise the follicular dendritic cells found in the germinal centre of a lymph node, inter-digitating dendritic cells found in the periphery of a lymph node, and Langerhans cells found in the epithelia [1]. Langerhans cell sarcoma (LCS) is a rare malignant tumour of langerhans cells.
Langerhans cell tumours are classified by the World Health Organisation (WHO) into Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH) [2]. LCH is a clinically benign disease, however rarely can transform into LCS [3]. LCS displays features typical of malignant tumours i.e. rapid growth, local invasion, the ability to recur and metastasise. Langerhans cells can be distinguished by their morphology (characteristic longitudinally grooved nuclei and with the presence of Birbeck granules) and immunohistochemical profile CD1a+ve, S100+ve, CD21−ve, CD35−ve and CD68−ve [4]. The differentiation between the two is based on characteristic cytological findings; LCS is characterised by malignant cytological features eg. atypia, and number of mitoses present. A positive immunohistochemical staining for CD1a, CD207 (Langerin) and S-100 protein are confirmatory of LCS [5], [6].
Given its rarity, it is unsurprising that there is a lack of evidence regarding the most appropriate treatment for this condition. Also, since the pathophysiology of LCS is poorly understood, most of the treatment protocols remain empirical and combination of surgery and chemoradiotherapy produce an unpredictable response. Further difficulty is encountered in searching for historical data as the nomenclature for both histiocytic and dendritic cell neoplasms has changed through time: LCS was previously named malignant histiocytosis X, which should be differentiated from malignant histiocytosis (a syndrome of systemic proliferation of atypical histiocytes). Therefore the aim of this work was to review, compile, analyse and present clinical details including the management and outcomes of this challenging disease entity.
Section snippets
Materials and methods
We conducted a systematic literature search on 21st September 2014 of MEDLINE (1966 to September 2014), CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Clinical Trials, without language restriction for studies including combined key terms and exploded Medical Subject Headings of the terms: (“langerhans cell sarcoma”[MeSH Terms] OR (“langerhans”[All Fields] AND “cell”[All Fields] AND “sarcoma”[All Fields]) OR “langerhans cell sarcoma”[All Fields]) OR
Results
The abstracts for 510 articles were reviewed. Of these 459 were excluded, including 5 whose full text was not in English with insufficient data in the abstract for inclusion, leaving 51 articles. Accessing the references of these yielded 7 more articles. Fifty-eight papers underwent full text review of which a further 12 were excluded (Fig. 1). In total 46 studies were included in the final analysis yielding 66 cases presented in Table 1. Lucas et al. [8] was found to be an update on a
Discussion
LCS is a rare disease with a generally poor prognosis. Our understanding of its pathogenesis is a function of its rarity and compounds the difficulty in establishing optimum management. The pattern of presentation broadly fits with the hypothesis of disease starting most commonly in the skin or mucosa where Langerhans cell are most prevalent, with initial spread via the local lymphatics prior to further dissemination. This would seem appropriate given the known role of Langerhans cells in
Conclusion
In summary a review of all the cases in the literature suggests an improved overall survival compared to previous estimates with patients with single-organ disease being at an apparent advantage. Due to the small number of patients it is inherently difficult to draw firm conclusions however multi-modality management appears to be more effective, with surgery most effective if clear margins can be obtained (Fig. 3). Adjuvant therapy, if planned, should not be delayed. There is no absolute
Conflict of interest
None to declare.
Funding resources
Not required.
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These authors contributed equally to this work.