Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?

Abstract

Langerhans cell histiocytosis (LCH) is the unifying designation for a rare proliferative disorder that occurs predominantly in childhood and involves the main antigen-presenting cell of the epidermis. LCH can present in a multitude of ways, from a self-limited rash that resolves spontaneously to a systemic multi-organ disease with a 20% mortality rate. Because some forms behave in a relatively benign manner and are associated with an inflammatory cell infiltrate, it has been proposed that LCH might be a reactive disease. However, its neoplastic nature is suggested by the fact that the proliferating cells in LCH are clonal and overexpress p53. Nonetheless, no recurrent genomic, genetic or epigenetic abnormalities have been identified. Instead, a variety of molecular abnormalities that are consistent with disordered Langerhans cell maturation have been described. A faithful small animal model would aid our understanding of the pathophysiology of LCH but, to date, none exists. Challenges to the creation of a model include the lack of characteristically recurrent genetic abnormalities and the absence of a truly tissue-specific promoter to drive expression of genetic elements solely in Langerhans cells. Still, some of the phenotypic abnormalities in adhesion molecule or chemokine receptor expression might be modeled with sufficient precision to allow the testing of novel therapies.

Langerhans' cell histiocytosis

“…Вопрос о том, явля ется ли ЛКЛ реактивным процессом или злокачест венным опухолевым заболеванием, в настоящее вре мя является предметом дискуссий [6].…”

Does Adjunctive Chemotherapy Reduce Remission Rates Compared to Cortisone Alone in Unifocal or Multifocal Histiocytosis of Bone?

“…Although the stem cell has been identified, the pathogenesis remains unclear [10,23]. While it has been suggested LCH is a primary neoplastic disorder of the LC [29], more recent evidence points toward an immunologic aberration [2,5,10]. LCH can occur at any age but is predominantly seen in children and in males [27].…”

VEGF and p53 Biomarkers in Pediatric Patients With Langerhans Cell Histiocytosis

“…2 Current treatments ensure 2-year survival rates exceeding 99%. 3 According to the World Health Organization committee on Histiocytic/Reticulum Cell proliferations, LCH is categorized as single system with 1 site, single system with multiple site involvement (multifocal), and those with multisystem disease. 4 The single system involvement is often a self-limiting disease, but multisystem involvement means one third of patients will have organ dysfunction and poor prognosis.…”

“…Skin and bone are the commonest sites of involvement. 3 A younger age at diagnosis correlates with severe disease, but histology of lesions cannot predict multisystem disease. 1 Rather, the clinical picture is determined by the location and the extent to which the body sites are infiltrated by Langerhans cells, with involvement of risk organs (liver, lungs, and bone marrow) considered as an adverse prognostic factor.…”

“…Serious complications such as diabetes insipidus from invasion of the pituitary stalk or respiratory failure due to pulmonary involvement can occur. 3 Twenty percent of the multisystem cases with organ failure are not responsive to treatment and would be fatal 5 ; even the multisystem disease with no organ failure would leave the subject with significant disabilities. 6 p53 is one of the tumor suppressor genes located on the short arm of chromosome 17.…”