Tumour Review
Langerhans cell sarcoma: A systematic review

https://doi.org/10.1016/j.ctrv.2015.02.011Get rights and content

Highlights

  • Overall disease specific survival was 27.2 months (18.3 months disease-free).

  • Surgery has a role in localised disease where the aim is to obtain clear margins.

  • Further research is required to obtain a consensus on chemotherapeutic regimen.

  • Multi-modality management appears more effective than mono-therapy.

  • Bone marrow transplant appears the most reliable treatment of disseminated disease.

Abstract

Langerhans cell sarcoma (LCS) is a rare malignant tumour of Langerhans cells with a poor outcome. Given its rarity, there is a lack of evidence regarding the most appropriate treatment for this condition. Therefore the aim of this work was to review, compile, analyse and present clinical details and to determine the optimal treatment regimen.

A search of PubMed, CINAHL, EMBASE, Cochrane, CENTRAL, clinicaltrials.gov and Google Scholar was supplemented by hand searching. Data extracted included demographics, treatment, type of LCS and clinical outcome. Of 510 citations identified by a systematic literature search, 46 case series including 66 subjects with LCS met criteria for analysis.

The most common treatment modality was chemotherapy, used alone or in combination in 47 cases (71%) followed by surgery in 31 cases (47%). Overall mean (S.E.) disease specific survival and disease free survival were 27.2 (3.9) and 18.3 (3.8) months respectively. There was a significant difference in both disease specific and disease free survival between the local, loco-regional and disseminated disease cohorts (DSS p = 0.014; DFS p < 0.001).

More localised disease confers a survival advantage. Multi-modality therapy appears to be most effective, with the addition of radiotherapy to chemotherapy appearing beneficial. Complete surgical excision with clear margins being most effective for local disease control. Any adjuvant therapy should not be delayed. Bone marrow transplant appears to be the most reliable treatment in terms of outcome especially in disseminated disease however has well known patient selection and toxicity/tolerance issues. The role of cell surface markers for prognostication remains unclear.

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.

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