Langerhans Cell Histiocytosis: Story of The Orphan Disease Beyond Dermatology

Langerhans cell histiocytosis (LCH), a rare proliferative disorder of cells that share phenotypic characteristics with dermal Langerhans cells, has long been considered an “orphan,” or neglected disease. Prior to its current designation, LCH was known as Hand–Schuller–Christian disease, Letterer–Siwe disease, or eosinophilic granuloma, which was combined under the umbrella designation of Histiocytosis X. The pathogenesis of LCH has remained unclear since the initial reports approximately 100 years earlier, and gene expression studies have demonstrated that these tumors do not originate from dermal Langerhans cells. It remains unclear whether LCH is reactive or neoplastic, although these tumors manifest a unique self-healing phenomenon that is rare among malignancies. The clinical presentation of LCH varies according to the involved organ/system, including common manifestations such as otitis media or pneumothorax or unusual manifestations such as diabetes insipidus. Accordingly, LCH cases are classified according to the number of involved organs/systems and sites, as well as the involvement of so-called “risk organs”. This review aimed to highlight recent insights as a better understanding of LCH will lead to more effective therapies.