Introduction

Central nervous system (CNS) involvement has been a well-known feature of Langerhans cell histiocytosis (LCH) since the early descriptions of the disease. Around the turn of the twentieth century, Hand–Schüller–Christian reported on patients with diabetes insipidus (DI), the clinical symptom of the most frequent type of CNS involvement (Schüller, 1915; Christian, 1920; Hand, 1921). Some years later, several authors described cases with ‘generalized xanthomatosis of Schüller–Christian type’ with cerebral involvement other than the infundibular region including isolated or multiple tumours, or demyelination, nerve cell destruction, and gliosis associated with a plethora of neurological symptoms (Chester and Kugel, 1932; Chiari, 1933; Davison, 1933; Feigin, 1956). During the last decade, in parallel to the more frequent routine use of modern imaging techniques, more and more LCH patients have been detected with CNS changes, some even in the absence of clinical symptoms (Greenwood et al., 1981; Graif and Pennock, 1986; Burn et al., 1992; Breidahl et al., 1993; Grois et al., 1993; Barthez et al., 2000). Magnetic resonance imaging (MRI) (or sometimes computed tomography, CT) is usually performed to monitor craniofacial lesions, or to evaluate patients with clinical endocrine deficiencies such as DI, growth retardation or pubertal abnormalities, or those with neurological or psychological problems.

As discussed later, histopathologically CNS involvement takes two forms, granulomas which morphologically and immunohistochemically are typical LCH lesions, and a neurodegenerative form in which no active LCH can be found.