INTRODUCTION

The World Health Organization currently classifies Langerhans cell derived neo­plasms as Langerhans cell histiocytosis and Langerhans cell sarcoma (Jaffe et al. 2007). Langerhans cell histiocytosis is a proliferating disorder of Langerhans cells, whereas Langerhans cell sarcoma is a neoplastic proliferation of Langerhans cells that have overtly malignant cytologic features (Ben-Ezra et al.1991, Jaffe et al. 2007). First diagnosed in 1984 (Wood et al.1984),Langerhans cell sarcoma is a very rare disease that can present de novo or progress from an antecedent Langerhans cell histiocytosis (Lee et al.2006). The diagno­sis relies on malignant cytological fea­tures, a typical immuno­phenotype that consistently shows ex­pression of CD1a, S-100 protein, and Langerin (CD207), and the appearance of the typical Birbeck granules demon­strated by electron mi­croscopy (Ferringer et al. 2006, Jaffe et al. 2007). In practice, Birbeck granules could be dem­onstrated only in a minority of cases due to the un­availability of fresh tissues for ultrastruc­tural analysis. Furthermore, cells may lose their ultrastructural characteris­tics as they become less differentiated. In a re­cent study, Verdijk et al (Verdijk et al. 2005)found lack of Birbeckgranules in Langerhans cells to be associated with mutation in the Langerin gene.

Currently, with the availability of antibo­dies suitable for tissue immunohistoche­mistry, the identification of the cell of ori­gin of the different types of tumours can easily be performed on formalin-fixed paraffin-embedded tissues. In addition, the use of antigen retrieval techniques has allowed an expanded range of mole­cules, previously detectable on fresh material only, to be studied in these tis­sues. Immunohistochemistry on paraffin-embedded tissues now play a major role in the diagnosis of Langerhans cell sar­coma, a diagnosis that has frequently been missed in the past.

In this report, we describe the histo­morphological and immunohistochemical findings of a Langerhans cell sarcoma in a 31-year-old man in the absence of ul­trastructural analysis.

CASE REPORT

The patient was a 31-yr-old male who presented with localized back pain at the mid-thoracic region for two months. It was associated with poor appetite and weight loss. The disease was progres­sive and had caused bilateral lower limb weakness and inability to walk. Past medical history showed that the patient had type 2 diabetes mellitus since he was 25 years of age.    

A magnetic resonance imaging (MRI) scan revealed a pathological fracture of the eighth thoracic vertebra (T8) asso­ciated with a heterogeneous lesion in­volving the body and both pedicles, and narrowing of the spinal cord canal (Figure 1A and 1B). A computed tomographic (CT) scan guided biopsy of the lesion was performed and was sent for histo­pathological examination.

Histologically, the biopsy showed frag­ments of tissue infiltrated by aggregates of large cells with overtly malignant fea­tures. The cells contained abundant eosinophilic cytoplasm with markedly pleomorphic nu­clei, some displaying prominent nucleoli (Figure 2). Abnormal mitotic figures were frequently seen and many multinucleated giant cells were present. There were scat­tered neutro­phils and eosinophils in the background (Figure 2). Immunohisto­chemical studies showed that the malig­nant cells ex­pressed CD1a, S100, CD68 and CD4 (Figure 2). The tu­mour cells were nega­tive for CD20, CD3, CD15, CD30, CK, MPO, HMB45 and Desmin. The antibod­ies used and the results obtained are summa­rized in Table 1. A combination of both the mor­phological and immunohis­tochemical findings supported the diag­nosis of Langerhans cell sarcoma.

The patient underwent anterior and posterior instrumentation decompres­sion and fusion procedures after which he symptomatically improved. He was sub­sequently planned for radiotherapy.

DISCUSSION

Langerhans cell sarcoma is a rare tu­mour and most previous reports have been in the form of case reports with paucity of infor­mation from larger series of cases (Mardones et al. 2009, Takahara et al. 2009). Tani et al (Tani et al. 1992) sug­gested that the diagnosis of malignant Langer­hans cell neoplasm should be made on the basis of the pres­ence of proliferation of Birbeck granule-containing tumor cells that have overt malignant cytological fea­tures such as nuclear atypia and fre­quent mitosis.

Ultrastructural analysis using electron microscope to demonstrate Birbeck granules in the cytoplasm of tumour  cells however requires fresh tissue that are fixed in suitable fixatives such as glu­taraldehye. Attempts at demonstrating Birbeck granules using formalin-fixed tissue samples were often unsuccessful (Lee et al. 2006, Zhao et al. 2009) due to fixation-related tissue ultrastructural damage. In the present case, the tissue sample was small and was entirely fixed in formalin and paraffin embedded, ren­dering it un­suitable for ultrastructural analysis. The diagnosis of Langerhans cell neoplasms had been previously made without the demonstration of Bir­beck granules in the tumour cells (Ben-Ezra et al. 1991, Lee et al. 2006). Ben-Ezra et al. (1991) could demonstrate Bir­beck granules in only three of the nine cases they reported.

Fortunately, with the advent of newer and better monoclonal antibodies for im­munohistochemistry, a new marker (i.e., CD1a) that is specific for Langer­hans cells is now available (Favara et al. 1997, Krenacs et al. 1993). CD1a repre­sents one of the first phases of differen­tiation of the CD1 antigen family. It is expressed on cell surfaces of cortical thymocytes and Langerhans cells (Krenacs et al. 1993), but it is not ex­pressed on other non-neoplastic macro­phages and den­dritic cells such as inter­digitating dendritic cells, follicular den­dritic cells and plas­macytoid dendritic cells (Jaffe et al. 2007). The narrow specificity of the anti­body (Krenacs et al. 1993) and the ease of the immune stain­ing process renders CD1a immunostain­ing useful as a routine procedure for the diagnosis of Langer­hans cell sarcoma (Nezelof & Basset 1998).

In addition to CD1a, the tumour consis­tently expresses S100 and Langerin (CD207). Interestingly, it can cause aber­rant expression of the T cell marker CD4 (as shown in the present case) but the markers of the B and T cell lineages were absent. The immunophenotype of Langerhans cell sarcoma is identical to that of Langerhans cell histiocytosis (Jaffe et al. 2007). Pathologically, the differentiation between these two condi­tions is purely morphological. Neverthe­less, Langer­hans cell sarcoma is associ­ated with an aggressive clinical course and distant metastasis (Ben-Ezra et al. 1991, Misery et al. 2003, Tani et al. 1992) and should be considered as a separate entity from Langerhans cell histiocytosis (Ben-Ezra et al. 1991, Jaffe et al.  2007, Tani et al. 1992).