General consideration

The etiology of LCH is unknown. LCH cells are clonal (except primary pulmonary LCH) [Willman et al 1994; Yousem et al 2001] and a cancer-associated mutation (BRAFV600E) was found in more than half of investigated specimens, indicating that LCH may be more a neoplastic (not a malignant!) disease than a reactive disorder, but the pathogenesis is still unclear [Badalian-Very et al 2010; Badalian-Very et al 2013]. Although apparent associations between LCH and malignant tumors have been recognized, these cases represent a minority of all LCH patients and the pathophysiologic relationship remains undefined [Egeler et al 1993].

The disease may affect any organ or system, more frequently bones, skin, and pituitary gland. Lymph nodes, liver, spleen, gut, the central nervous system, pituitary, and the hematopoietic system are less frequently affected. Lungs may be affected simultaneously or consecutively with other organs, but isolated pulmonary LCH (PLCH) occurs frequently in adults and may proceed to multisystem involvement. PLCH requires a different management in contrast to multi-organ involvement and is therefore discussed in a separate section.

Clinical manifestations of LCH vary depending on the organ or system affected, from self-healing disease to chronic recurrences. A rapid progressive form, seen in children, is usually not observed in adults. Langerhans cell sarcoma (malignant histiocytosis) can occur de novo or from an antecedent LCH [Lee et al 2006]. This paper will not cover other histiocytic disorders such as Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD) or malignant histiocytosis. In cases of occurrence of LCH and ECD or RDD in the same patient, the management is based on the predominant disease.

Treatment options vary depending on disease extent and severity at onset. A uniform diagnostic work-up is necessary. One of the main problems of LCH in adults is the variety of potentially involved organs resulting in several physicians being consulted. Frequently only the most obviously affected site is considered and a complete examination is not done thus missing other sites of disease.